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Biomedical subjects

J M Provenzale

Publications and source records attributed to J M Provenzale.

At least 19 recordsLinked to original sources
PubMed2001

MRI correlates of suicide attempt history in unipolar depression.

BACKGROUND: Suicide represents a major health problem in the United States, and prediction of suicide attempts is difficult. No structural neuroimaging studies have been done to specifically examine findings in patients who have attempted suicide. The objective of this study was to compare MRI findings in unipolar patients with and without a history of a suicide attempt. METHODS: In this post hoc analysis, 20 unipolar subjects with a history of a suicide attempt were matched by age and gender to unipolar subjects without a history of an attempt. Subjects were also matched on parameters such as cardiovascular history, electroconvulsive treatment history, and history of psychosis. Subjects with a history of any neurologic condition were excluded. There were no significant differences in age of onset of depression, number of episodes of depression, and Hamilton Depression scores between the two groups. T2-weighted magnetic resonance imaging (MRI) scans were rated using the Coffey and Boyko rating scales. RESULTS: Unipolar patients with a history of a suicide attempt demonstrated significantly more subcortical gray matter hyperintensities compared with patients without such a history. CONCLUSIONS: Patients with abnormal MRI findings may be at higher risk for mood disorders and suicide attempts because of disruption of critical neuroanatomic pathways. Gray matter hyperintensities in the basal ganglia may be especially associated with risk for suicide attempts.

Aged↗
PubMed2001

Evidence of white matter tract disruption in MRI hyperintensities.

BACKGROUND: Diffusion tensor imaging (DTI) of brain tissue measures the apparent diffusion coefficient (ADC), or isotropic diffusion, and anisotropy, or diffusion as influenced by tissue structure. We hypothesized that hyperintensities, when compared with normal tissue by DTI, would show evidence of damage through an increased ADC and decreased anisotropy. We also hypothesized that DTI changes in hyperintensities would be similar between depressed subjects and control subjects. METHODS: Fourteen depressed geriatric patients and nineteen control subjects received DTI. The ADC and aniso-tropy of normal tissue from standard regions were compared with hyperintensities from these regions. The Students' t test compared individual regions and averaged white matter results. RESULTS: Hyperintensities showed higher ADC and lower anisotropy than normal regions. Gray matter exhibited similar trends. There was no significant difference in diffusion characteristics of hyperintensities between subjects and control subjects. CONCLUSIONS: Hyperintensities damage the structure of brain tissue, and do so comparably in depressed subjects and control subjects.

Aged↗
PubMed2001

Long term response in a patient with neoplastic meningitis secondary to melanoma treated with (131)I-radiolabeled antichondroitin proteoglycan sulfate Mel-14 F(ab')(2): a case study.

Even with novel chemotherapeutic agents and external beam radiation therapy, the prognosis of neoplastic meningitis secondary to malignant melanoma is still dismal. The authors report a case study of a 46-year-old white female who presented with progressive hearing loss, severe headaches, nausea, vomiting, and a rapid decline in neurologic status. She was referred to Duke University Medical Center after conventional chemotherapy for malignant melanoma failed. She was enrolled in a Phase I trial of (131)I-labeled monoclonal antibody Mel-14 F(ab')(2) fragment administered intrathecally. Within a year after her treatment, she recovered, having a normal neurologic exam except for residual bilateral hearing loss. The authors discuss dosimetry, preclinical, and clinical studies conducted with Mel-14 F(ab')(2) and introduce a potentially promising therapy option in the treatment of neoplastic meningitis in patients with malignant melanoma. Currently, the patient remains neurologically normal except for a mild bilateral hearing loss more than 4 years after treatment and has no radiographic evidence of neoplastic meningitis.

Antibodies, Monoclonal↗
PubMed2001

Human herpesvirus 6 limbic encephalitis after stem cell transplantation.

Central nervous system complications are common in stem cell transplant recipients, but selective involvement of the medial temporal area is unusual. The 5 patients reported here presented after stem cell transplantation with increased hippocampal T2 signal on magnetic resonance imaging and increased hippocampal glucose uptake on [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) associated with short-term memory loss, insomnia, and temporal lobe electrographic seizure activity. The initial scalp electroencephalograms (EEGs) failed to detect seizure activity in these patients, although the memory dysfunction along with the magnetic resonance imaging and FDG-PET findings suggested subcortical seizure activity. However, extended EEG monitoring revealed repetitive temporal lobe electrographic seizure activity. Follow-up MRIs in 2 patients and postmortem findings on 1 patient suggested that hippocampal sclerosis had developed following the clinical syndrome. Cerebrospinal fluid studies revealed the presence of human herpesvirus 6, variant B, DNA in all of 3 patients who had lumbar punctures. Immunohistochemical staining for the P41 and P101 human herpesvirus 6 protein antigens showed numerous immunoreactive astrocytes and neurons in the hippocampus of 1 of the patients who died from other causes. Because of its subtle clinical presentation, this syndrome may be underrecognized, but can be diagnosed with appropriate magnetic resonance imaging techniques, EEG monitoring, and cerebrospinal fluid viral studies.

Adolescent↗
PubMed2001

Cerebral abscesses: investigation using apparent diffusion coefficient maps.

The combination of high signal and reduced apparent diffusion coefficients (ADC) within abscesses on diffusion-weighted MRI (DWI) has been reported as characteristic of abscesses, and useful for distinguishing them from cystic or necrotic neoplasms. To assess whether these are consistent findings in abscesses, we used DWI-derived ADC to investigate changes in water diffusibility in cerebral abscesses. We reviewed the MRI studies and clinical records of five patients with brain abscesses, who underwent DWI. Regions of interest were drawn within the abscesses on ADC maps, to obtain the ADC. The center of all five abscesses gave signal higher than that of white matter on DWI. The three largest also appeared bright on ADC maps, i. e., showed ADC substantially lower than those of normal white matter, consistent with restricted diffusion. However, the two smaller abscesses were not visible on ADC maps because their ADC were essentially the same as that of white matter; they did not show restricted diffusion. The absence of restricted diffusion within small abscesses may be related to intrinsic differences in molecular microenvironment between small and large abscesses, or to greater influence of volume averaging with surrounding edema on the ADC in smaller abscesses.

Brain Abscess↗
PubMed2001

Practical injection-rate CT perfusion imaging: deconvolution-derived hemodynamics in a case of stroke.

Previously reported methods of dynamic, contrast-enhanced, CT perfusion imaging in acute stroke have been promising but substantially limited by their dependence on very rapid rates of injection (typically 10-20 ml/s in an arm vein). Newly available deconvolution software permits the use of lower rates of injection (e. g., 3-4 ml/s), and rapidly provides maps of cerebral blood flow, cerebral blood volume and mean transit time. We report the potential of CT perfusion imaging performed with an injection rate of 4 ml/s to provide information on the extent of hemodynamic abnormality, and to help distinguish viable from nonviable ischemic tissue. The slower injection rates permitted by deconvolution analysis substantially enhance the practicality of CT perfusion imaging for studying stroke.

Brain↗
PubMed2001

Magnetic resonance imaging applications in the evaluation of tumor angiogenesis.

Angiogenesis, the growth of new blood vessels, is a critical component in the development of solid tumors. Over the last decade, progress in the study of the biology of angiogenesis has led to identification of a large number of molecules that promote, participate, and regulate the growth of new vessels in normal tissue and in tumors. Consequently, many new targets for suppression of angiogenesis have been identified and are now at various stages of development and evaluation in clinical trials. Magnetic resonance imaging (MRI) provides an attractive tool for in vivo analysis of the basic biology of angiogenesis, for preclinical evaluation of the activity of a number of potential antiangiogenic agents, as well as for clinical detection, diagnosis, and prognosis. One of the features of MRI is the wide range of physiologic parameters by which angiogenesis can be imaged. This review presents the biological basis of angiogenesis with emphasis on characteristics of the neovasculature that can be used for imaging, followed by an overview of the MRI approaches that are being evaluated for the analysis of tumor angiogenesis.

Blood Volume↗
PubMed2001

Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas.

Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide (TEMO) have been shown in independent studies to prolong survival of patients with recurrent malignant glioma following surgery and radiotherapy. On the basis of preclinical evidence of synergism between Gliadel wafers and TEMO, a phase I study was designed to evaluate the toxicity of combining these 2 agents in the treatment of patients with recurrent supratentorial malignant glioma. All patients had surgical resection of the tumor at relapse, and up to 8 Gliadel (3.85%) wafers were placed in the surgical cavity following resection. Two weeks after surgery, TEMO was given orally daily for 5 days. Cohorts of 3 patients received TEMO at daily doses of 100 mg/m2, 150 mg/m2, and 200 mg/m2, respectively. Patients were assessed for toxicity 4 weeks after start of the first course of TEMO. Contrast-enhanced MRI of the brain was used to assesstumor response after the first cycle of TEMO. Patients with stable disease or response after the first cycle of TEMO were allowed to continue treatment at the same dose every 4 weeks for 12 cycles or until disease progression or unacceptable toxicity. Ten patients with a median age of 47 years (range, 22-66 years) were enrolled in this study. There were 7 patients with glioblastoma multiforme and 3 patients with anaplastic astrocytoma. Three patients were treated with TEMO at the first dose level of 100 mg/m2, 4 at the second dose level of 150 mg/m2, and 3 at the third dose level of 200 mg/m2. The 10 patients received a median of 3 cycles (range, 1-12 cycles) of TEMO following placement of Gliadel wafers. The treatment was well tolerated, with only 1 patient suffering grade III thrombocytopenia at the highest dose level. Two patients at each dose level had no evidence of disease progression after treatment. Four patients suffered progressive disease on therapy. Our study demonstrates that TEMO can be given safely after placement of Gliadel (3.85%) wafers. The recommended dosage for TEMO for a phase II study of this combination is 200 mg/m2 per day for 5 days.

Adult↗
PubMed2001

Use of exponential diffusion imaging to determine the age of ischemic infarcts.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) detects acute ischemic infarcts with high lesion conspicuity. Determination of infarct age is difficult on DWI alone because infarct signal intensity (SIinfarct) on DWI is influenced by T2 properties ("T2 shine-through"). Maps of the apparent diffusion coefficient (ADC) reflect pure diffusion characteristics without T2 effects but have low lesion conspicuity. Thus, in clinical practice, combined use of DWI and ADC maps is required. Exponential DWI (eDWI) is an innovative means of MRI-diffusion data analysis that merges the advantages of DWI and ADC maps. The authors hypothesized that SIinfarct on eDWI would correlate with infarct age. The authors studied 114 consecutive patients who had 120 ischemic strokes with clearly determined onset times and who underwent echo-planar DWI. The eDWI were generated by dividing the signal intensity on DWI by that on the corresponding T2 image on a pixel-by-pixel basis. SIinfarct on eDWI was measured in the lesion core and expressed as a percentage of contralateral control tissue. On eDWI, relative SIinfarct changed significantly with infarct age (P < .0001). When patients were sorted in infarct-age groups, no significant differences were found within the first 120 hours. However, for patients studied within 5 days, the mean relative SIinfarct was significantly higher compared with patients studied > or = 8 days after stroke (P < .05). For all infarcts up to 5 days old, the eDWI signal intensity was higher than control tissue (hyperintense appearance). All infarcts > 10 days old had an eDWI signal intensity lower than control tissue (hypointense appearance). The authors concluded that the use of eDWI, as a single set of images, reliably differentiates acute infarcts (< or = 5 days old) from infarcts > 10 days old. This feature would be expected to be helpful when the distinction between acute and nonacute infarction cannot be determined on clinical grounds.

Adolescent↗
PubMed2001

Evaluation of white matter anisotropy in Krabbe disease with diffusion tensor MR imaging: initial experience.

PURPOSE: To compare diffusion tensor magnetic resonance imaging with conventional T2-weighted imaging for evaluation of white matter changes in patients with Krabbe disease. MATERIALS AND METHODS: In eight patients with Krabbe disease and eight age-matched control subjects, anisotropy maps were generated with diffusion tensor data by using echo-planar imaging with diffusion gradient encoding in six directions. Anisotropy maps and T2-weighted images were visually inspected. Relative anisotropy (RA) and normalized T2-weighted signal intensity in white matter tracts and gray matter nuclei were quantitatively compared between patients and controls (paired Student t test). RESULTS: Loss of diffusion anisotropy appeared on anisotropy maps as areas of decreased hyperintensity in patients with Krabbe disease. Differences in RA between Krabbe disease patients and control subjects were significant in eight of nine white matter structures studied (P =.001-.01) and in basal ganglia (P =.04). T2-weighted signal intensity was also significantly different in the same white matter structures (P =.006-.049) but not in basal ganglia. In the three patients imaged after stem cell transplantation, mean RA was between the RAs of untreated patients and control subjects. CONCLUSION: Diffusion tensor-derived anisotropy maps (a) provide a quantitative measure of abnormal white matter in patients with Krabbe disease, (b) are more sensitive than T2-weighted images for detecting white matter abnormality, and (c) may be a marker of treatment response.

Anisotropy↗
PubMed2001

Increased brain apparent diffusion coefficient in children with neurofibromatosis type 1.

PURPOSE: To describe the changes in brain water diffusibility in five anatomic locations in children with neurofibromatosis type 1 (NF 1) compared with these changes in control subjects and to describe the water diffusibility changes associated with hyperintense basal ganglia lesions in children with NF 1. MATERIALS AND METHODS: Twenty highly related pairs of children consisting of one child with NF 1 and one unaffected child were examined. Prospective comparisons of isotropic apparent diffusion coefficient (ADC) values at five anatomic locations were performed, with and without T2-hyperintense lesions included. Retrospective analysis of hyperintense globus pallidus lesions in 16 children and in the paired control subjects also was performed. RESULTS: Significant increases in ADC values were seen in all five anatomic locations in the NF 1 group. The greatest increases were seen in the globus pallidus (14%; P =.002) and brachium pontis (10.8%; P =.003). With exclusion of hyperintense lesions, significant ADC increases were measured in four locations. Significant ADC increases were seen in hyperintense globus pallidus lesions in the NF 1 group compared with ADC values in the normal-appearing contralateral globus pallidus (4.9%; P =.02) and those in the globus pallidus of the paired control subjects (16%; P =.003). CONCLUSION: Significant ADC increases were measured both in the hyperintense lesions and in the normal-appearing areas of the brain in children with NF 1.

Adolescent↗
PubMed2001

Serial MR imaging of pineal cysts: implications for natural history and follow-up.

OBJECTIVE: The purpose of this study was to examine the frequency of change in size of pineal cysts on serial MR studies. MATERIALS AND METHODS: Thirty-two patients (19 females, 13 males) with a diagnosis of pineal cyst at any time who underwent brain MR imaging more than once in a period of at least 6 months were identified by computerized search of radiology reports. Four patients underwent MR imaging to follow up pineal cysts, whereas the remaining patients were imaged for a variety of indications, including intracerebral neoplasms. Measurements of maximal cyst dimension on both initial and latest follow-up studies were obtained in all patients, and cyst volumes were calculated in 23 patients. RESULTS: Length of follow-up ranged from 6 months to 9 years. All cysts were considered incidental and none were treated. Maximal cyst dimensions ranged from 0.5 to 2.2 cm. On average, there was no significant change in cyst volume. The maximal dimension of the cyst did not change in 24 (75%) of 32 patients. Two cysts resolved completely on follow-up, three cysts decreased by 2-4 mm, two cysts enlarged by 2-3 mm, and one cyst formed and grew to 1.2 cm. CONCLUSION: Whereas the size of pineal cysts as a whole remained unchanged on serial MR studies, cysts may either form or involute in individual patients. Small increases in cyst size did occur but were not associated with specific clinical findings. These findings suggest that typical pineal cysts may be followed up on a clinical basis alone rather than on imaging.

Adult↗
PubMed2001

(18)F-fluorodeoxyglucose positron emission tomography and MR imaging findings in Rasmussen encephalitis.

BACKGROUND AND PURPOSE: Rasmussen encephalitis is a chronic, progressive encephalitis that manifests as an abrupt-onset, intractable seizure disorder in previously developmentally normal children. The objectives of the current study were to characterize the (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and MR imaging findings in Rasmussen encephalitis and to test the hypotheses that data from both imaging techniques are required to establish the diagnosis and identify the affected cerebral hemisphere in some cases. METHODS: Eleven patients with Rasmussen encephalitis were identified from a review of a computer database. The MR (n = 10) and PET (n = 11) imaging data were reviewed retrospectively and conjointly. RESULTS: On MR images, nine of 10 patients manifested bilateral cerebral atrophy that predominantly involved one hemisphere. One patient had purely unilateral cerebral atrophy. We observed foci of abnormally increased T2 signal intensity in nine of 10 patients. On FDG PET images, all patients showed extensive regions of hypometabolism within the cerebral hemisphere that showed the greatest atrophy. Discrete foci of hypermetabolism, indicative of seizure activity, were observed in six patients. The FDG PET and MR imaging findings were either stable or gradually progressive in patients with multiple imaging studies (MR, n = 5; FDG PET, n = 5). CONCLUSION: Rasmussen encephalitis is characterized by diffuse, unilateral cerebral hypometabolism on FDG PET images, with corresponding regions of cerebral atrophy on MR images. Although MR imaging data alone are sufficient to suggest a diagnosis of Rasmussen encephalitis in many cases, correlation with FDG PET data increases diagnostic confidence and allows the unequivocal identification of the affected cerebral hemisphere in patients whose MR imaging findings are subtle or distributed bilaterally.

Adolescent↗
PubMed2001

Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome.

BACKGROUND AND PURPOSE: Previous studies have shown that lesions in posterior reversible encephalopathy syndrome are often isointense on diffusion-weighted MR images. We hypothesized that 1) apparent diffusion coefficient (ADC) maps using various thresholds would show larger abnormalities in posterior white matter (WM) and 2) isointense appearance of lesions on isotropic diffusion-weighted images results from a balance of T2 prolongation effects and diffusibility effects. METHODS: T2-weighted MR images from 11 patients were reviewed. Hyperintense lesions were located in both anterior and posterior WM in eight patients and solely in posterior WM in three patients. The ADC maps were produced by use of ADC values > or = 3 SD and > or = 10 SD above the mean value of normal WM. Lesions on diffusion-weighted images were classified as isointense or hypointense. ADC values within lesions (ADC(L)) were compared with those of normal WM (ADC(N)), and compared for isointense lesions and hypointense lesions. RESULTS: The distribution of lesions with ADC values > or = 3 SD was essentially identical to that on T2-weighted images. Regions with ADC values > or = 10 SD were found in both anterior WM and posterior WM in two patients and solely in posterior WM in nine patients. On diffusion-weighted images, lesions appeared isointense in seven patients and hypointense in four patients. Mean ADC(L)/ADC(N) for all lesions was 1.81; for hypointense lesions, 2.30. CONCLUSION: Vasogenic edema was more severe in posterior WM. Isointense lesions result from a balance of T2 effects and increased water diffusibility. Hypointense lesions have higher ADC values, which are not balanced by T2 effects.

Adult↗
PubMed2000

Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment. PATIENTS AND METHODS: In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of (131)I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment. RESULTS: We treated 42 patients with (131)I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively. CONCLUSION: The MTD for administration of (131)I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis.

Adult↗
PubMed2000

Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine (O(6)-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial of carmustine (BCNU) plus O(6)-BG to define the toxicity and maximum-tolerated dose (MTD) of BCNU in conjunction with the preadministration of O(6)-BG with recurrent or progressive malignant glioma. PATIENTS AND METHODS: Patients were treated with O(6)-BG at a dose of 100 mg/m(2) followed 1 hour later by BCNU. Cohorts of three to six patients were treated with escalating doses of BCNU, and patients were observed for at least 6 weeks before being considered assessable for toxicity. Plasma samples were collected and analyzed for O(6)-BG, 8-oxo-O(6)-BG, and 8-oxoguanine concentration. RESULTS: Twenty-three patients were treated (22 with glioblastoma multiforme and one with anaplastic astrocytoma). Four dose levels of BCNU (13.5, 27, 40, and 55 mg/m(2)) were evaluated, with the highest dose level being complicated by grade 3 or 4 thrombocytopenia and neutropenia. O(6)-BG rapidly disappeared from plasma (elimination half-life = 0. 54 +/- 0.14 hours) and was converted to a longer-lived metabolite, 8-oxo-O(6)-BG (elimination half-life = 5.6 +/- 2.7 hours) and further to 8-oxoguanine. There was no detectable O(6)-BG 5 hours after the start of the O(6)-BG infusion; however, 8-oxo-O(6)-BG and 8-oxoguanine concentrations were detected 25 hours after O(6)-BG infusion. The mean area under the concentration-time curve (AUC) of 8-oxo-O(6)-BG was 17.5 times greater than the mean AUC for O(6)-BG. CONCLUSION: These results indicate that the MTD of BCNU when given in combination with O(6)-BG at a dose of 100 mg/m(2) is 40 mg/m(2) administered at 6-week intervals. This study provides the foundation for a phase II trial of O(6)-BG plus BCNU in nitrosourea-resistant malignant glioma.

Adult↗