Biomedical subjects

James S Babb

Publications and source records attributed to James S Babb.

At least 37 records · Page 2Linked to original sources

PubMed2005

Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies.

BACKGROUND: Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies. METHODS: Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence. RESULTS: The median follow-up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow-up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression-free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis. CONCLUSIONS: Hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Importance of small (< or = 20-mm) enhancing lesions seen only during the hepatic arterial phase at MR imaging of the cirrhotic liver: evaluation and comparison with whole explanted liver.

PURPOSE: To retrospectively assess the importance and imaging appearance of small (< or = 20 mm in diameter) hepatic arterial phase-enhancing (HAPE) lesions that are occult during portal and/or equilibrium phases and at unenhanced T1- and T2-weighted magnetic resonance (MR) imaging and to determine the gross pathologic diagnosis with whole-liver explant comparison. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and compliant with HIPPA. Forty-six patients with cirrhosis who underwent MR imaging and transplantation within 90 days were evaluated with breath-hold T2-weighted and volumetric three-dimensional gadolinium-enhanced gradient-echo MR imaging in the hepatic arterial, portal venous, and equilibrium phases at 1.5 T. Three readers, who were blinded to the pathologic results, retrospectively reviewed the MR images in consensus for small HAPE nodules that were occult at T2-weighted and portal and/or equilibrium phase MR imaging. Only patients with nodules that enhanced during the arterial phase were included in the final study group, which included 16 patients (12 men and four women) aged 18-66 years (median age, 51.5 years). Explanted livers were serially sliced into 5-8-mm-thick sections to evaluate dysplastic nodules and hepatocellular carcinomas (HCCs). The Fisher exact test was performed to determine whether there was a relationship between HCC and the presence of a neoplastic HAPE-only lesion. The Mann-Whitney test was used to determine if patients with at least one neoplastic HAPE-only lesion had a larger number of non-HAPE-only lesions. RESULTS: The 16 patients had 45 HAPE-only lesions; three (7%) of which were neoplastic, including one overt HCC, one HCC arising in a dysplastic nodule, and one dysplastic nodule. None of the remaining 42 HAPE-only lesions (93%) had correlative pathologic findings. All three neoplastic lesions seen only during the arterial phase were found in eight patients with concomitant HCC, who also had an additional 13 pathologically proved nonneoplastic HAPE-only lesions. In eight patients without HCC, none of the HAPE-only lesions were neoplastic. A concomitant non-HAPE-only neoplastic lesion was not a significant (P = .2) predictor for the presence of at least one neoplastic HAPE-only lesion. There was a preliminary but insignificant (P = .13) indication that the number of non-HAPE-only lesions tends to be higher in patients with neoplastic HAPE-only lesions. CONCLUSION: The majority (93%) of HAPE-only lesions that are occult at T2-weighted and portal and/or equilibrium phase MR imaging are nonneoplastic, even in patients with pathologically proved HCC.

Adolescent↗

PubMed2005

Correlation of apparent diffusion coefficient with neuropsychological testing in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Patients with nonlesional temporal lobe epilepsy have long been known to have abnormalities of memory. Recently, these patients have been shown to have increased diffusivity in the hippocampus. We hypothesized that in these patients, a negative correlation would exist between diffusivity measures of the mesial temporal lobe and performance on neuropsychological tests. METHODS: Twenty presurgical patients with temporal lobe epilepsy and 20 age- and sex-matched healthy controls underwent MR imaging of the brain. Apparent diffusion coefficient region of interest measures were taken in both hippocampi and parahippocampal gyri by 2 independent observers. Mean whole brain diffusivity was calculated. All patients completed neuropsychological testing. Electroencephalogram and pathology results were collected. Patients and controls were compared with respect to each apparent diffusion coefficient measure. In patients, apparent diffusion coefficients ipsilateral and contralateral to the seizure focus were compared. Associations were assessed between diffusivity measures and neuropsychological scores. RESULTS: Eleven patients had right-sided seizure foci and 9 had left-sided seizure foci. Patients demonstrated higher apparent diffusion coefficient values than controls over the whole brain, in the hippocampi, and in the parahippocampal gyri (P < .05). Patients demonstrated higher apparent diffusion coefficient within the ipsilateral hippocampus (1.19 +/- 0.22 x 10(-3) s/mm2) and parahippocampal gyrus (1.02 +/- 0.12 x 10(-3) s/mm2) compared with the contralateral side (1.02 +/- 0.16 x 10(-3) s/mm2 and 0.96 +/- 0.09 x 10(-3) s/mm2, respectively) (P < .05). Negative correlations were seen between hippocampal apparent diffusion coefficients and multiple memory tests (P < .05). CONCLUSION: Quantitative diffusion measurements in the hippocampus correlate with memory dysfunction in patients with temporal lobe epilepsy.

Adult↗

PubMed2005

Assessing global invasion of newly diagnosed glial tumors with whole-brain proton MR spectroscopy.

BACKGROUND AND PURPOSE: Because of their invasive nature, high-grade glial tumors are uniformly fatal. The purpose of this study was to quantify MR imaging-occult, glial tumor infiltration beyond its radiologic margin through its consequent neuronal cell damage, assessed by the global concentration decline of the neuronal marker N-acetylaspartate (NAA). METHODS: Seventeen patients (10 men; median age, 39 years; age range, 23-79 years) with radiologically suspected (later pathologically confirmed) supratentorial glial neoplasms, and 17 age- and sex-matched controls were studied. Their whole-brain NAA (WBNAA) amounts were obtained with proton MR spectroscopy: for patients on the day of surgery (n = 17), 1 day postsurgery (n = 15), and once for each control. To convert into concentrations, suitable for intersubject comparison, patients' global NAA amounts were divided by their brain volumes segmented from MR imaging. Least squares regression was used to analyze the data. RESULTS: Pre- and postoperative WBNAA (mean +/- SD) of 9.2 +/- 2.1 and 9.7 +/- 1.8 mmol/L, respectively, in patients were indistinguishable (P = .369) but significantly lower than in controls (12.5 +/- 1.4 mmol/L). Mean resected tumor size (n = 15) was approximately 3% of total brain volume. CONCLUSION: The average 26% WBNAA deficit in the patients, which persisted following surgical resection, cannot be explained merely by depletion within the approximately 3% MR imaging-visible tumor volume or an age-dependent effect. Although there could be several possible causes of such widespread decline--perineuronal satellitosis, neuronal deafferentation, Wallerian and retrograde degeneration, vasogenic edema, functional diaschisis, secondary vascular changes--most are a direct or indirect reflection of extensive, MR imaging-occult, microscopic tumor cell infiltration, diffusely throughout the otherwise "normal-appearing" brain.

Adult↗

PubMed2004

Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia.

Animal models of ovarian cancer are crucial for understanding the pathogenesis of the disease and for testing new treatment strategies. A model of ovarian carcinogenesis in the rat was modified and improved to yield ovarian preneoplastic and neoplastic lesions that pathogenetically resemble human ovarian cancer. A significantly lower dose (2 to 5 mug per ovary) of 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the one ovary to maximally preserve its structural integrity. DMBA-induced mutagenesis was additionally combined with repetitive gonadotropin hormone stimulation to induce multiple cycles of active proliferation of the ovarian surface epithelium. Animals were treated in three arms of different doses of DMBA alone or followed by hormone administration. Comparison of the DMBA-treated ovaries with the contralateral control organs revealed the presence of epithelial cell origin lesions at morphologically distinct stages of preneoplasia and neoplasia. Their histopathology and path of dissemination to other organs are very similar to human ovarian cancer. Hormone cotreatment led to an increased lesion severity, indicating that gonadotropins may promote ovarian cancer progression. Point mutations in the Tp53 and Ki-Ras genes were detected that are also characteristic of human ovarian carcinomas. Additionally, an overexpression of estrogen and progesterone receptors was observed in preneoplastic and early neoplastic lesions, suggesting a role of these receptors in ovarian cancer development. These data indicate that this DMBA animal model gives rise to ovarian lesions that closely resemble human ovarian cancer and it is adequate for additional studies on the mechanisms of the disease and its clinical management.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2004

Relapsing-remitting multiple sclerosis: metabolic abnormality in nonenhancing lesions and normal-appearing white matter at MR imaging: initial experience.

PURPOSE: To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. RESULTS: Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). CONCLUSION: Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter.

Adult↗

PubMed2004

Defining intrahepatic biliary anatomy in living liver transplant donor candidates at mangafodipir trisodium-enhanced MR cholangiography versus conventional T2-weighted MR cholangiography.

PURPOSE: To compare three-dimensional (3D) mangafodipir trisodium-enhanced T1-weighted magnetic resonance (MR) cholangiography with conventional T2-weighted MR cholangiography for depiction and definition of intrahepatic biliary anatomy in liver transplant donor candidates. MATERIALS AND METHODS: One hundred eight healthy liver transplant donor candidates were examined with two MR cholangiographic methods. All candidates gave written informed consent, and the study was approved by the institutional review board. First, breath-hold transverse and coronal half-Fourier single-shot turbo spin-echo and breath-hold oblique coronal heavily T2-weighted turbo spin-echo sequences were performed. Second, mangafodipir trisodium-enhanced breath-hold fat-suppressed 3D gradient-echo sequences were performed through the ducts (oblique coronal plane) and through the entire liver (transverse plane). Interpretation of biliary anatomy findings, particularly variants affecting right liver lobe biliary drainage, and degree of interpretation confidence at both 3D mangafodipir trisodium-enhanced MR cholangiography and T2-weighted MR cholangiography were recorded and compared by using the Wilcoxon signed rank test. Then, consensus interpretations of both MR image sets together were performed. Intraoperative cholangiography was the reference-standard examination for 51 subjects who underwent right lobe hepatectomy. The McNemar test was used to compare the accuracies of the individual MR techniques with that of the consensus interpretation of both image sets together and to compare each technique with intraoperative cholangiography. RESULTS: Biliary anatomy was visualized with mangafodipir trisodium enhancement in all patients. Mangafodipir trisodium-enhanced image findings agreed with findings seen at combined interpretations significantly more often than did T2-weighted image findings (in 107 [99%] vs 88 [82%] of 108 donor candidates, P < .001). Confidence was significantly higher with the mangafodipir trisodium-enhanced images than with the T2-weighted images (mean confidence score, 4.5 vs 3.4; P < .001). In the 51 candidates who underwent intraoperative cholangiography, mangafodipir trisodium-enhanced imaging correctly depicted the biliary anatomy more often than did T2-weighted imaging (in 47 [92%] vs 43 [84%] donor candidates, P = .14), whereas the two MR imaging techniques combined correctly depicted the anatomy in 48 (94%) candidates. CONCLUSION: Mangafodipir trisodium-enhanced 3D MR cholangiography depicts intrahepatic biliary anatomy, especially right duct variants, more accurately than does conventional T2-weighted MR cholangiography.

Adolescent↗

PubMed2004

Myocardial infarction: optimization of inversion times at delayed contrast-enhanced MR imaging.

Seventeen patients underwent magnetic resonance (MR) imaging for myocardial viability with a protocol approved by the institutional review board and gave written informed consent. Breath-hold cine inversion-recovery segmented k-space true fast imaging with steady-state precession sequence, referred to as inversion time (TI) mapping, was performed to determine optimal TI for myocardial infarction inversion-recovery imaging. From TI mapping, optimal TI was 180-315 msec 10-15 minutes after administration of 0.15 mmol/kg of gadolinium-based contrast material. At that optimal TI, relative signal intensity of infarcted myocardium compared with uninfarcted myocardium was maximal (mean +/- standard deviation, 297.8% +/- 86.5), whereas signal-to-noise ratio of uninfarcted myocardium was minimal (4.5 +/- 1.2). When applied to conventional myocardial infarction inversion-recovery imaging, optimal TI resulted in nulling of signal intensity of uninfarcted myocardium in all patients and in excellent conspicuity of infarcted myocardium in all nine patients with visible infarction.

Adult↗

PubMed2004

Patient characteristics compete with dose as predictors of acute treatment toxicity in early phase clinical trials.

PURPOSE: The purpose of this study was to identify patient characteristics that may be risk factors or markers of susceptibility to adverse treatment effects in cancer Phase I and II clinical trials. PATIENTS AND METHODS: A total of 459 patients enrolled in 23 therapeutic Phase I and II studies at the Fox Chase Cancer Center were included in the analysis. Patient-specific characteristics, medical and treatment history, doses of experimental agents, and graded toxicities were extracted from case report forms. We developed a novel summary measure, the toxicity index (TI), to better discriminate patients on the basis of their overall toxicity experiences. Mixed model ANOVA was used to model TI on the basis of data from all trials using a specific agent. Generalized estimating equations in the context of binary logistic regression were used to model dose-limiting toxicity. RESULTS: Seventeen pretreatment factors, including performance status, alkaline phosphatase, total bilirubin, serum creatinine, and tobacco use, emerged as significant predictors of toxicity as defined by dose-limiting toxicity or TI. Unexpectedly, dose was not always a predictor of toxicity. Even for values within the normal range, the TI identified serum bilirubin and alkaline phosphatase as predictors of toxicity after treatment with docetaxel and alkaline phosphatase as a predictor for toxicity after treatment with irinotecan. CONCLUSIONS: Independent of dose, certain pretreatment characteristics, including measures of organ function that are in the normal range, were found to be predictors of treatment toxicity. Because of its sensitivity to differences in overall toxicity, the TI should prove to be a useful tool for identifying predictors of chemotherapy-related toxicity.

Adult↗

PubMed2004

Promoter hypermethylation profile of kidney cancer.

PURPOSE: Promoter hypermethylation is an important mechanism of inactivation of tumor suppressor genes in cancer cells. Kidney tumors are heterogeneous in their histology, genetics, and clinical behavior. To gain insight into the role of epigenetic silencing of tumor suppressor and cancer genes in kidney tumorigenesis, we determined a hypermethylation profile of kidney cancer. EXPERIMENTAL DESIGN: We examined the promoter methylation status of 10 biologically significant tumor suppressor and cancer genes in 100 kidney tumors (50 clear cell, 20 papillary, 6 chromophobe, 5 collecting duct, 5 renal cell unclassified, 7 oncocytoma, 6 transitional cell carcinomas of the renal pelvis, and 1 Wilms' tumor) by methylation-specific PCR. The hypermethylation profile was examined with regard to clinicopathological characteristics of the kidney cancer patients. RESULTS: Hypermethylation of one or more genes was found in 93 (93%) of 100 tumors. A total of 33% of kidney tumors had one gene, 35% two genes, 14% three genes, and 11% four or more genes hypermethylated. The frequency of hypermethylation of the 10 genes in the 100 tumor DNAs was VHL 8% (all clear cell), p16(INK4a) 10%, p14(ARF) 17%, APC 14%, MGMT 7%, GSTP1 12%, RARbeta2 12%, RASSF1A 45%, E-cadherin 11%, and Timp-3 58%. Hypermethylation was observed in all of the histological cell types and grades and stages examined. No hypermethylation was observed in specimens of normal kidney or ureteral tissue from 15 patients. Hypermethylation of VHL was specific to clear cell tumors. RASSF1A methylation was detected at a significantly higher frequency in papillary renal cell tumors and in high-grade tumors of all cell types. MGMT methylation was more frequent in nonsmokers. Simultaneous methylation of five or more genes was observed in 3 (3%) of 100 tumors and may indicate a methylator phenotype in kidney cancer. In addition, the CpG island in the promoter of the fumarate hydratase (FH) tumor suppressor gene was bisulfite sequenced and was found to be unmethylated in 15 papillary renal tumors. CONCLUSIONS: Promoter hypermethylation is common, can occur relatively early, may disrupt critical pathways, and, thus, likely plays an important role in kidney tumorigenesis. A hypermethylation profile may be useful in predicting a patient's clinical outcome and provide molecular markers for diagnostic and prognostic approaches to kidney cancer.

Adult↗

PubMed2004

Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated.

PURPOSE: Ionizing radiation can reduce tumor growth outside the field of radiation, known as the abscopal effect. Although it has been reported in multiple malignancies, the abscopal effect remains a rare and poorly understood event. Ionizing radiation generates inflammatory signals and, in principle, could provide both tumor-specific antigens from dying cells and maturation stimuli that are necessary for dendritic cells' activation of tumor-specific T cells. We therefore tested the hypothesis that the abscopal effect elicited by radiation is immune mediated. This was directly tested by enhancing the number of available dendritic cells using the growth factor Flt3-Ligand (Flt3-L). METHODS AND MATERIALS: Mice bearing a syngeneic mammary carcinoma, 67NR, in both flanks were treated with Flt3-L daily for 10 days after local radiation therapy (RT) to only 1 of the 2 tumors at a single dose of 2 or 6 Gy. The second nonirradiated tumor was used as indicator of the abscopal effect. Data were analyzed using repeated measures regression. RESULTS: RT alone led to growth delay exclusively of the irradiated 67NR tumor, as expected. Surprisingly, growth of the nonirradiated tumor was also impaired by the combination of RT and Flt3-L. As control, Flt3-L had no effect without RT. Importantly, the abscopal effect was shown to be tumor specific, because growth of a nonirradiated A20 lymphoma in the same mice containing a treated 67NR tumor was not affected. Moreover, no growth delay of nonirradiated 67NR tumors was observed when T cell deficient (nude) mice were treated with RT plus Flt3-L. CONCLUSIONS: These results demonstrate that the abscopal effect is in part immune mediated and that T cells are required to mediate distant tumor inhibition induced by radiation.

Animals↗

PubMed2004

Individualized patient dosing in phase I clinical trials: the role of escalation with overdose control in PNU-214936.

PURPOSE: A patient-specific dose-escalation scheme using a Bayesian model of Escalation with Overdose Control (EWOC) was conducted to establish the maximum tolerated dose (MTD) of PNU-214936 in advanced non-small-cell lung cancer (NSCLC). PNU-214936 is a murine Fab fragment of the monoclonal antibody 5T4 fused to a mutated superantigen staphylococcal enterotoxin A (SEA). PATIENTS AND METHODS: Seventy-eight patients with NSCLC were treated with an individualized dose of PNU-214936 calculated using EWOC, based on their anti-SEA antibody level, and given as a 3-hour infusion on 4 consecutive days. RESULTS: Fever (82%; grade 3 to 4, 2.6%) and hypotension (57%; grade 3 to 4, 9%) were the most common toxicities. Eight dose-limiting toxicities occurred, as defined as any grade 4 toxicity occurring within the first 5 days. The MTD was defined as a function of pretreatment anti-SEA antibody level. MTD ranged from 103 ng/kg for patients with anti-SEA concentrations < or = 10 pmol/mL, to 601 ng/kg for patients with anti-SEA concentrations of 91 to 150 pmol/mL. A minor tumor response was demonstrated in five of 66 assessable patients. CONCLUSION: EWOC determined phase I doses of PNU-214936 that were adjusted for patient anti-SEA antibody level, while safeguarding against overdose. Furthermore, the method permitted the construction of a dosing algorithm that would allow patients in subsequent clinical investigations to be treated with a dose of PNU-214936 that is tailored to their specific tolerance for the agent, as reflected by their pretreatment anti-SEA.

Adult↗

PubMed2004

Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian surface epithelium.

The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17beta-estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and (3)H-thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury- or ovulation-induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation-associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations.

Animals↗

PubMed2004

Preferential occult injury of corpus callosum in multiple sclerosis measured by diffusion tensor imaging.

PURPOSE: To investigate the feasibility of diffusion tensor imaging (DTI) assessment of microscopic fiber tract injury in the corpus callosum (CC) and other normal-appearing white matter (NAWM) in patients with early multiple sclerosis (MS). MATERIALS AND METHODS: DTI was performed in 12 healthy volunteers and 15 patients who have relatively short disease duration (mean = 2.7 years). Both fractional anisotropy (FA) and mean diffusivity (MD) were obtained in different regions of normal-appearing CC (NACC) and NAWM in frontal and occipital regions. RESULTS: The data showed significantly lower FA (P < 0.001) and higher MD (P < 0.04) for NACC regions, but not for frontal and occipital NAWM regions, in patients than in those in healthy volunteers after Bonferroni adjustment. The increase of MD in the entire NACC regions was correlated with the total cerebral lesion volume (r = 0.75, P = 0.001) in patients. CONCLUSION: The water diffusion changes indicate that in the early phase of disease there is a preferential occult injury of CC, which is likely due to the Wallerian degeneration from distant lesions.

Adult↗

PubMed2004

Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter.

PURPOSE: To prospectively determine hemodynamic changes in the normal-appearing white matter (NAWM) of patients with relapsing-remitting multiple sclerosis (RR-MS) by using dynamic susceptibility contrast material-enhanced perfusion magnetic resonance (MR) imaging. MATERIALS AND METHODS: Conventional MR imaging (which included acquisition of pre- and postcontrast transverse T1-weighted, fluid-attenuated inversion recovery, and T2-weighted images) and dynamic susceptibility contrast-enhanced T2*-weighted MR imaging were performed in 17 patients with RR-MS (five men and 12 women; median age, 38.4 years; age range, 27.6-56.9 years) and 17 control patients (seven men and 10 women; median age, 42.0 years; age range, 18.7-62.5 years). Absolute cerebral blood volume (CBV), absolute cerebral blood flow (CBF), and mean transit time (MTT) (referenced to an arterial input function by using an automated method) were determined in periventricular, intermediate, and subcortical regions of NAWM at the level of the lateral ventricles. Least-squares regression analysis (controlled for age and sex) was used to compare perfusion measures in each region between patients with RR-MS and control patients. Repeated-measures analysis of variance and the Tukey honestly significant difference test were used to perform pairwise comparison of brain regions in terms of each perfusion measure. RESULTS: Each region of NAWM in patients with RR-MS had significantly decreased CBF (P <.005) and prolonged MTT (P <.001) compared with the corresponding region in control patients. No significant differences in CBV were found between patients with RR-MS and control patients in any of the corresponding areas of NAWM examined. In control patients, periventricular NAWM regions had significantly higher CBF (P =.03) and CBV (P =.04) than did intermediate NAWM regions. No significant regional differences in CBF, CBV, or MTT were found in patients with RR-MS. CONCLUSION: The NAWM of patients with RR-MS shows decreased perfusion compared with that of controls.

Adolescent↗

PubMed2004

Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade.

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) permit in vivo assessment of glioma microvasculature. We assessed the associations between rCBV and K(trans) derived from dynamic, susceptibility-weighted, contrast-enhanced (DSC) MR imaging and tumor grade and between rCBV and K(trans). METHODS: Seventy-three patients with primary gliomas underwent conventional and DSC MR imaging. rCBVs were obtained from regions of maximal abnormality for each lesion on rCBV color maps. K(trans) was derived from a pharmacokinetic modeling algorithm. Histopathologic grade was compared with rCBV and K(trans) (Tukey honestly significant difference). Spearman and Pearson correlation factors were determined between rCBV, K(trans), and tumor grade. The diagnostic utility of rCBV and K(trans) in discriminating grade II or III tumors from grade I tumors was assessed by logistic regression. RESULTS: rCBV was significantly different for all three grades (P </=.0005). K(trans) was significantly different between grade I and grade II or III (P =.027) but not between other grades or combinations of grades. Spearman rank and Pearson correlations, respectively, were as follows: rCBV and grade, r = 0.817 and r = 0.771; K(trans) and grade, r = 0.234 and r = 0.277; and rCBV and K(trans), r = 0.266 and r = 0.163. Only rCBV was significantly predictive of high-grade gliomas (P <.0001). CONCLUSION: rCBV with strongly correlated with tumor grade; the correlation between K(trans) and tumor grade was weaker. rCBV and K(trans) were positively but weakly correlated, suggesting that these parameters demonstrate different tumor characteristics. rCBV is a more significant predictor of high-grade glioma than K(trans).

Adolescent↗

PubMed2003

Communication of BRCA1 and BRCA2 results to at-risk relatives: a cancer risk assessment program's experience.

We describe results from a survey designed to assess patterns of communication within families shortly after an individual receives results of BRCA1 and BRCA2 mutation carrier status. Shortly after disclosure of BRCA1 and BRCA2 genetic test results, the proband was contacted by phone to administer the post disclosure survey. Questions asked included whether they had shared their results with their siblings or adult children, if there were difficulties in communicating the test results, and if there was any distress associated with the sharing of results. A total of 162 women who have received results from BRCA1 and BRCA2 genetic testing participated in the survey. The probands shared their results more often with their female than their male relatives (P < 0.001). Probands who had tested positive for a mutation in the BRCA1 or BRCA2 gene shared their results more often with their relatives than did probands who were not carriers (P = 0.002). Probands reported more often that their siblings rather than their adult children had difficulties understanding the results (P = 0.001). The probands who were carriers more often reported having difficulties explaining their results to their relatives (P < 0.001) and their relatives were upset on hearing the result more often than were the relatives of probands who were not carriers (P < 0.001). The probands who were carriers reported more often that they were upset explaining their results to their relatives than did the probands who were not carriers (P < 0.001). Individuals are disclosing their test results to their relatives. Probands who are BRCA1- or BRCA2-positive are more likely to experience difficulty and distress with the communication of their test results to family members.

Adolescent↗

PubMed2003

Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis.

It is well known that multiple sclerosis (MS) pathogenesis continues even during periods of clinical silence. To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of-interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0 cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40 +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho level was the only single metric differentiating patients from controls at 100% specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation, gliosis, or de- and remyelination in the NAWM. Both metabolites are potential prognostic indicators of current disease activity, preceding NAA decline and atrophy.

Adult↗