PubMed Health⌕ Search

Biomedical subjects

James M Provenzale

Publications and source records attributed to James M Provenzale.

At least 19 recordsLinked to original sources
PubMed2003

Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression.

Previous studies have shown a reduction of orbital frontal cortex volume and an increase in magnetic resonance imaging signal hyperintensities in geriatric depression. We aimed to assess the relationship between subcortical gray- and deep white-matter lesions and orbital frontal cortex volume in elderly depressives and controls. The study included 41 elderly depressed patients and 41 age-matched control subjects. The orbital frontal cortex volume was measured in both hemispheres using a standardized MRI procedure. Signal hyperintensities were rated on (T2)-weighted MRI with qualitative lesion analyses performed according to an established hyperintensity classification system. After controlling for total cerebral hemisphere, age and sex, the geriatric depressed subjects had significant reduction in orbital frontal cortex volume and compared with the control group. Multiple linear regression modeling indicated that reduced orbital frontal cortex volumes were significantly associated with increased subcortical gray-matter lesions. Our study confirmed the reduction of OFC volume in geriatric depressed subjects. We also suggest that subcortical lesions may decrease OFC volume. Further studies are needed to understand how subcortical lesions may be related to OFC volume changes.

Aged↗
PubMed2003

Lexical and sublexical components of age-related changes in neural activation during visual word identification.

Positron emission tomography data (Madden, Langley, et al., 2002) were analyzed to investigate adult age differences in the relation between neural activation and the lexical (word frequency) and sublexical (word length) components of visual word identification. The differential influence of these components on reaction time (RT) for word/nonword discrimination (lexical decision) was generally similar for the two age groups, with word frequency accounting for a greater proportion of lexical decision RT variance relative to word length. The influence of word length on RT, however, was relatively greater for older adults. Activation in regions of the ventral occipito-temporal cortex was related to the RT changes associated with word frequency and length for older adults, but not for younger adults. Specifically, older adults' frequency effects were related to activation in both anterior (Brodmann's area [BA] 37) and posterior (BAs 17 and 18) regions of the occipito-temporal pathway, whereas word length effects were only associated with posterior activation (BA 17). We conclude that aging affects the neural mechanisms supporting word identification performance although behavioral measures of this ability are generally constant as a function of age.

Adult↗
PubMed2003

Phase II trial of temozolomide in patients with progressive low-grade glioma.

PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. PATIENTS AND METHODS: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m(2)/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. RESULTS: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to infinity months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced > or = grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. CONCLUSION: Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Adolescent↗
PubMed2003

Localization of age-associated white matter hyperintensities in late-life depression.

OBJECTIVE: Deep white matter hyperintense lesions are associated with advanced age and late-life depression. The authors examined where age-related cerebral lesions occurred in elderly depressed and healthy control subjects. METHODS: Eighty-seven depressed subjects and 47 control subjects underwent 1.5 T cranial magnetic resonance imaging (MRI). Utilizing a semiautomated method, a segmented image was created containing only white matter lesions. We created a statistical parametric map (SPM) separately for each subject group that displayed the association between lesions in any voxel and advanced age. RESULTS: The SPM analysis in depressed subjects demonstrates a significant association between age and lesions found in bilateral, frontal, and left parietal regions. The analysis in control subjects found significant associations only in bilateral parieto-temporal regions, not frontal regions. CONCLUSIONS: This study demonstrates a different pattern of age-related lesion location between depressed and control subjects. It further supports the theory that frontostriatal disconnection contributes to late-life depression.

Age Factors↗
PubMed2003

Screening for cerebral metastases with FDG PET in patients undergoing whole-body staging of non-central nervous system malignancy.

PURPOSE: To compare fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) with the current standard, magnetic resonance (MR) imaging, to determine the sensitivity and specificity of FDG PET for detection of cerebral metastases and to determine the factors that may affect lesion conspicuity. MATERIALS AND METHODS: Forty patients underwent brain PET and contrast material-enhanced brain MR imaging, with a maximum of 30 days between examinations. PET and MR images were each retrospectively reviewed by two independent readers who were blinded to the clinical history and results of the other technique. Presence of metastatic disease was recorded for each modality. Sensitivity and specificity of FDG PET were determined with MR imaging as the standard. Statistical analysis was performed with the Fisher exact test and the logistic regression model. RESULTS: Sixteen patients had cerebral metastases at MR imaging, and in 12 of these, PET scans were interpreted as showing metastatic disease (in four, scans were false-negative). Twenty-four patients had no cerebral metastases at MR imaging, and 20 of these had PET scans interpreted as normal (in four, scans were false-positive). For identification of patients with cerebral metastases, FDG PET had a sensitivity of 75% (12 of 16) and a specificity of 83% (20 of 24). Thirty-eight metastatic lesions were seen at MR imaging; 23 (61%) of these were identified at PET. Size was a statistically significant factor that influenced lesion detection at PET (P <.001). CONCLUSION: Only 61% of metastatic lesions in the brain were identified at PET. In particular, detection of small lesions was difficult.

Adolescent↗
PubMed2003

Infarct volume on apparent diffusion coefficient maps correlates with length of stay and outcome after middle cerebral artery stroke.

BACKGROUND: Diffusion-weighted MRI (DWI) can depict acute ischemia based on decreased apparent diffusion coefficient (ADC) values. ADC maps, unlike DWI (which have contributions from T2 properties), solely reflect diffusion properties. Recent studies indicate that severity of neurological deficit corresponds with degree of ADC alteration. PURPOSE: To determine whether infarct volume on ADC maps correlates with length of hospitalization and clinical outcome in patients with acute ischemic middle cerebral artery (MCA) stroke. STUDY POPULATION: Forty-five consecutive patients with acute ( 3 SDs below the average ADC value of a contralateral control region. Infarct volume was correlated with length of hospitalization and 6-month outcome assessed with Glasgow Outcome Scale (GOS), Modified Rankin Score (mRS), Barthel Index (BI) and a dichotomized outcome status with favorable outcome defined as GOS 1, mRS or=95. RESULTS: Infarct volume on ADC maps ranged from 0.2 to 187 cm(3) and was significantly correlated with length of hospitalization (p < 0.001, r = 0.67). Furthermore, ADC infarct volume was significantly correlated with GOS (r = 0.73), mRS (r = 0.68), BI (r = 0.67) and outcome status (r = 0.65) (each p < 0.001). Multiple logistic regression revealed a statistically significant correlation between ADC infarct volume and outcome status (p < 0.05), but none for Canadian Neurological Scale score, age and gender (p >0.05 each). CONCLUSION: Infarct volume measured by using a quantitative definition for infarcted tissue on ADC maps correlated significantly with length of hospitalization (as a possible surrogate marker for short-term outcome) and functional outcome after 6 months. ADC infarct volume may provide prognostic information for patients with acute ischemic MCA stroke.

Aged↗
PubMed2003

Serial MR imaging of volumes of hyperintense white matter lesions in elderly patients: correlation with vascular risk factors.

OBJECTIVE: The purpose of the study was to examine change in volume of hyperintense white matter lesions in a cohort of community-dwelling elderly subjects without neuropsychiatric disease. SUBJECTS AND METHODS. One hundred seventeen volunteers underwent brain MR imaging on a 1.5-T scanner. Demographic data and the presence of specific medical illnesses were recorded at the time of the initial scanning. Hyperintense white matter lesion volume was measured using a supervised semiautomated technique that seeded lesions and then created a segmented lesion image. Subjects underwent repeated MR imaging at a mean of 25 months. Mean change in lesion volume and mean percentage of change were determined between the two time points. Logistic regression models were used to examine the differential effects of age, sex, race, and self-reported medical morbidity. RESULTS: Mean baseline volume of cerebral hyperintense lesions was 4.91 cc, and at 2-year follow-up, it was 6.42 cm(2) (p < 0.0001), for a mean increase of 26.7%. Comparable results were seen in separate analyses of hemispheric hyperintense lesion volumes. Neither sex, race, nor baseline hyperintense lesion volume was significantly associated with an interval increase in lesion volume. Age (p = 0.0117) and presence of diabetes (p = 0.0215) were associated with greater change. CONCLUSION: Elderly subjects exhibited approximately a 27% increase in hyperintense lesion volume over a 2-year period, a finding influenced by both age and medical comorbidity rates. Because hyperintense lesions can be associated with several neuropsychiatric conditions, further research is needed to determine if interventions designed to slow hyperintense lesion disease progression may improve neuropsychiatric outcomes.

Aged↗
PubMed2003

Quantitative assessment of the time course of infarct signal intensity on diffusion-weighted images.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MR imaging is important in evaluating acute stroke, and knowledge of the signal intensity changes associated with acute stroke is valuable. Our purpose was to model the time course of the signal intensity of infarcts and to characterize the apparent diffusion coefficient (ADC) and T2 effects on total signal intensity. METHODS: Ninety-two patients were included in this prospective cross-sectional study. Signal intensity in infarcts (4 hours to 417 days) and control regions were recorded on DW images (b = 0 and 1000 s/mm(2)), ADC maps, and ratio images (image with b = 1000 s/mm(2) divided by image with b = 0 s/mm(2)). Cubic spline functions were used for polynomial fitting. The time courses of log signal intensity with log time were modeled. The independent contributions of T2 and ADC to the total signal intensity were retrospectively compared at 0-63 hours, 3-10 days, 11-57 days, and 57 days onward. RESULTS: Mean signal intensity on DW images was maximal at 40 hours after infarction and normalized at 57 days. At 0-63 hours, the positive effect of ADC on signal intensity was greater than that of T2 (log value,13 +/- 0.04 vs 0.11 +/- 0.05; P =.04). At days 3-10, the positive T2 effect predominated (0.13 +/- 0.08 vs 0.08 +/- 0.04; P =.12). At 10-57 days, the positive T2 effect was greater than the negative ADC effect. After day 57, the negative ADC effect predominated. CONCLUSION: The signal intensity of infarcts on DW images normalizes at 57 days, which is substantially later than previously suggested. T2 (shine-through) effect contributes largely to the total infarct signal intensity.

Acute Disease↗
PubMed2002

Development of a semi-automated method for quantification of MRI gray and white matter lesions in geriatric subjects.

Brain magnetic resonance imaging (MRI) allows for quantitative assessment of hyperintense foci, which are seen with aging and various diseases. These foci, considered to represent lesions, are important in the study of various psychiatric illnesses, including depression. Few quantitative measures have been developed for such research. The goal of the current study was to develop a reliable and efficient method for quantifying the volumes of gray and white matter lesions in MRI scans of the elderly. Interrater reliability was determined by repeat lesion measures on 16 scans. Semi-automated segmentation was performed that identified potential lesions, and then lesions were manually selected based upon detailed anatomic criteria. The lesion quantification procedure took between 25 and 45 min per scan. Reliability intraclass correlation coefficients (ICCs) were 0.99 for both gray and white matter lesions. Volumetric results were found to be moderately correlated with previous lesion ratings (r-values between 0.37 and 0.62, P<0.0001). Among the 700 scans processed with this method, lesion volumes ranged from 0 to 7.3 ml for gray matter, and from 0.4 to 96.8 ml for white matter. Our method proved to be efficient and reliable for quantifying lesions in MRI scans of the elderly.

Aged↗
PubMed2002

Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype.

The purpose of the study was to consider MRI hyperintensities as a potential endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a candidate gene for BPD. MRI scans were performed on 21 members of a family with a high incidence of BPD. Two-point and multipoint linkage analyses were performed and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members had MRI hyperintensities, including all bipolar patients and six family members with no affective illness. Two-point linkage analysis yielded negative results for all models. Multipoint linkage analysis yielded negative results except for Model 1a, in which a maximal LOD score was -1.24. A mutation screen of Exons 3 and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this family.

Adolescent↗
PubMed2002

Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma.

PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent malignant glioma resistant to nitrosoureas. PATIENTS AND METHODS: Patients were treated with O(6)-BG at an intravenous dose of 120 mg/m(2) followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week intervals. RESULTS: Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hematopoietic toxicity. Twelve patients experienced reversible > or = grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/- 1.7 microg/mL/h v 5.0 +/- 1.3 microg/mL/h) of O(6)-BG for patients receiving phenytoin and those not treated with this drug. CONCLUSION: These results indicate that O(6)-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection.

Adult↗
PubMed2002

Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity (131)I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase II trial, 120 mCi of (131)I-labeled murine 81C6 was injected directly into the surgically created resection cavity of 33 patients with previously untreated malignant glioma (glioblastoma multiforme [GBM], n = 27; anaplastic astrocytoma, n = 4; anaplastic oligodendroglioma, n = 2). Patients then received conventional external-beam radiotherapy followed by a year of alkylator-based chemotherapy. RESULTS: Median survival for all patients and those with GBM was 86.7 and 79.4 weeks, respectively. Eleven patients remain alive at a median follow-up of 93 weeks (range, 49 to 220 weeks). Nine patients (27%) developed reversible hematologic toxicity, and histologically confirmed, treatment-related neurologic toxicity occurred in five patients (15%). One patient (3%) required reoperation for radionecrosis. CONCLUSION: Median survival achieved with (131)I-labeled 81C6 exceeds that of historical controls treated with conventional radiotherapy and chemotherapy, even after accounting for established prognostic factors including age and Karnofsky performance status. The median survival achieved with (131)I-labeled 81C6 compares favorably with either (125)I interstitial brachy-therapy or stereotactic radiosurgery and is associated with a significantly lower rate of reoperation for radionecrosis. Our results confirm the efficacy of (131)I-labeled 81C6 for patients with newly diagnosed malignant glioma and suggest that a randomized phase III study is indicated.

Adult↗
PubMed2002

Subcortical white matter lesions and functional impairment in geriatric depression.

Geriatric depression is associated with significant functional impairment. There is also growing evidence linking vascular brain changes to depression in late life. We sought to examine the relationship between cerebrovascular disease and impairment in basic activities of daily living (BADL) and instrumental activities of daily living (IADL) in a group of older depressives. The sample consisted of 224 depressed adults aged 60 years and above enrolled in Duke's Mental Health Clinical Research Center. All subjects had unipolar major depression and were free of other major psychiatric and neurological illness, including dementia. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Geriatric psychiatrists assessed cognition using the Mini Mental State Examination (MMSE) and depression severity using the Montgomery Asberg Depression Rating Scale (MADRS). Subjects had a standardized magnetic resonance imaging (MRI) brain scan. MRI scans were processed using a semi-automated method to determine volumes of subcortical white matter lesions (WML) and subcortical gray matter lesions (GML). Logistic regression was used to examine effects of WML and GML controlling for demographic and clinical factors. Greater volume of WML was associated with impairment in both BADL and IADL, while GML was associated with IADL impairment. In logistic models, WML remained significantly associated with IADL after controlling for the effects of age, gender, depression severity, and medical comorbidity. We concluded that white matter lesions are independently associated with functional impairment. Further studies are needed to understand how these lesions affect function, e.g., through effects on cognition or motor skills.

Activities of Daily Living↗
PubMed2002

Adult age differences in visual word identification: functional neuroanatomy by positron emission tomography.

Adult age differences in the neural systems mediating semantic (context-independent) memory were investigated using positron emission tomography (PET). Younger (20-29 years) and older (62-70 years) participants performed lexical decision (word/nonword discrimination) and nonsemantic (simple visual search) baseline tasks during PET scanning. Within the lexical decision task, display duration and presentation rate were varied across scans. The behavioral data suggested that although an age-related slowing was evident in visual feature and response processing, the retrieval of semantic/lexical information was similar for younger and older adults. For both age groups, lexical-related activation occurred in inferior prefrontal and occipitotemporal regions of the left hemisphere. Differential activation, as a function of age group, was observed in the left occipitotemporal pathway as a result of older adults' maintaining higher levels of neural activity in striate cortex (during visual search) and in inferior temporal cortex (during lexical decision). The prefrontal activation was similar for the two age groups. Thus, although this form of semantic memory retrieval does not undergo significant age-related decline, an age-related change in the associated pattern of neural activation is evident. These findings differ from previous neuroimaging studies of episodic (context-dependent) memory retrieval, which have suggested that age-related compensatory mechanisms are expressed primarily by greater activation of prefrontal regions for older adults than for younger adults.

Adult↗
PubMed2002

Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI evidence and unanswered questions.

Whether or not severe febrile seizures in infancy cause hippocampal injury and subsequent medial temporal sclerosis is an often debated question in epilepsy. Recent magnetic resonance imaging (MRI) of infants suffering from febrile seizures has provided preliminary evidence that abnormally increased T2 signal intensity can be seen in the hippocampi of infants following prolonged and focal febrile seizures. Follow-up MRIs in a few of these infants have confirmed that medial temporal sclerosis can develop following these acute MRI signal changes. In this article, we review the hypotheses and MRI evidence relating to hippocampal injury during prolonged febrile seizures and the later development of medial temporal sclerosis.

Animals↗
PubMed2002

Hypointense thrombus on T2-weighted MR imaging: a potential pitfall in the diagnosis of dural sinus thrombosis.

PURPOSE: To determine the frequency of hypointense appearance of dural sinus thrombosis on T2-weighted images, which may mimic a normal flow void, and when possible correlate with appearance on T1-weighted images. METHODS AND MATERIALS: Retrospective review of radiology files showed 51 patients with a discharge diagnosis of dural sinus thrombosis who underwent MR imaging during the period 1986-1998. These images were reviewed by an experienced neuroradiologist for appearance on T2-weighted images. This process yielded five cases in which a hypointense appearance on this pulse sequence simulated a normal flow void. An additional two cases were added from the teaching files of two other institutions giving a total of seven cases (13% of studies). The resulting study population consisted of five women and two men (mean age 27.1 years). T1 weighted images were available in five patients. In two patients MR venography was available, but not T1-weighted images. The diagnosis of dural sinus thrombosis was based solely on absence of flow void on T1-weighted images in one case, solely on absence of flow void on MR venography in two cases and absence of flow void on T1-weighted images in conjunction with MR venography or gradient echo findings in 4 patients. All images were obtained on a 1.5 T magnet (GE Medical Systems; Milwaukee, Wisconsin). RESULTS: In all patients hypointense signal of thrombus was isointense with normal flow voids in other dural sinuses on T2-weighted images. In all cases in which T1-weighted images were available, the signal intensity of thrombus was isointense to gray matter. CONCLUSION: Hypointense appearance of thrombus on T2-weighted images is a potential pitfall in the MR diagnosis of dural sinus thrombosis. Because thrombus in this stage of evolution appears isointense to gray matter on T1-weighted images, careful attention must be paid to other sequences to avoid this pitfall.

Adolescent↗
PubMed2002

Aging and attentional guidance during visual search: functional neuroanatomy by positron emission tomography.

Positron emission tomography (PET) was used to examine adult age differences in neural activation during visual search. Target detection was less accurate for older adults than for younger adults, but both age groups were successful in using color to guide attention to a subset of display items. Increasing perceptual difficulty led to greater activation of occipitotemporal cortex for younger adults than for older adults, apparently as the result of older adults maintaining higher levels of activation within the easier task conditions. The results suggest that compensation for age-related decline in the efficiency of occipitotemporal cortical functioning was implemented by changes in the relative level of activation within this visual processing pathway, rather than by the recruitment of other cortical regions.

Adult↗