Retrospective measurement of the diffusion tensor eigenvalues from diffusion anisotropy and mean diffusivity in DTI.

A simple theoretical framework to compute the eigenvalues of a cylindrically symmetric prolate diffusion tensor (D) from one of the rotationally-invariant diffusion anisotropy indices and average diffusivity is presented and validated. Cylindrical or axial symmetry assumes a prolate ellipsoid shape (lambdaparallel=lambda1>lambdaperpendicular=(lambda2+lambda3)/2; lambda2=lambda3). A prolate ellipsoid with such symmetry is largely satisfied in a number of white matter (WM) structures, such as the spinal cord, corpus callosum, internal capsule, and corticospinal tract. The theoretical model presented is validated using in vivo DTI measurements of rat spinal cord and human brain, where eigenvalues were calculated from both the set of diffusion coefficients and a tensor analysis. This method was used to retrospectively analyze literature data that reported tensor-derived average diffusivity, anisotropy, and eigenvalues, and similar eigenvalue measurements were obtained. The method provides a means to retrospectively reanalyze literature data that do not report eigenvalues. Other potential applications of this method are also discussed.     

Diffusion tensor imaging of in vivo and excised rat spinal cord at 7 T with an icosahedral encoding scheme.

Regional values of fractional anisotropy (FA) and mean diffusivity (D(av)) of in vivo and excised rat spinal cords were measured using an iscosahedral encoding scheme that is based on 21 uniformly distributed and alternating gradient directions with an echo planar imaging (EPI) readout. Based on the water phantom studies, this scheme was shown to provide unbiased estimation of FA. The stability of the scanner during the acquisition of diffusion tensor imaging (DTI) data was evaluated. Repeated measurements of the FA values demonstrated excellent reproducibility, as assessed by the Bland-Altman analysis. These studies demonstrated a reduced anisotropy in excised samples relative to in vivo cords. Diffusion in the spinal cord gray matter was shown to be anisotropic. The FA value in the dorsal white matter (WM) was found to be higher relative to the ventral WM. Results from these studies should provide the necessary baseline data for serial in vivo DTI of injured spinal cord.     

Aggressive venous neointimal hyperplasia in a pig model of arteriovenous graft stenosis

BACKGROUND: Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of well over one billion dollars per annum. Venous neointimal hyperplasia characterized by stenosis and subsequent thrombosis, is the major cause of polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem, there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts. We believe that this is partly due to the lack of a validated large animal model of arteriovenous stenosis that could be used to test out novel interventions. METHODS: Seven-centimeter PTFE loop grafts were placed between the femoral artery and vein of domestic pigs. The grafts were removed at 2, 4, 7, 14 and 28 days after surgery and subjected to a detailed histological and immunohistochemical examination. RESULTS: Significant neointimal hyperplasia and venous stenosis developed by 28 days at the graft-vein anastomosis. There was minimal neointimal hyperplasia at the graft-artery anastomosis. Venous neointimal hyperplasia (VNH) was characterized by (a) the presence of smooth muscle cells/myofibroblasts; (b) angiogenesis within both the neointima and adventitia; and (c) the presence of an active macrophage cell layer lining the PTFE graft material. These results are very similar to the human lesion previously described by us in dialysis patients. CONCLUSIONS: We have developed and validated a pig model of venous neointimal hyperplasia that is very similar to the human lesion. We believe that this is an ideal model in which to test out novel interventions for the prevention and treatment of clinical hemodialysis vascular access dysfunction.     

Inhaled nitric oxide in the preoperative evaluation of pulmonary hypertension in heart transplant candidates

OBJECTIVE: The goal of this study was to evaluate the efficacy of 100% oxygen and inhaled nitric oxide (iNO) in decreasing pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) in dilated cardiomyopathy patients being evaluated for orthotopic heart transplantation (OHT); who, despite maximal intravenous (IV) dilator therapy, had persistent moderate-to-severe pulmonary hypertension. DESIGN: A prospective nonrandomized clinical study. SETTING: University hospital, major transplant center. PARTICIPANTS: Twenty-one adult patients undergoing OHT evaluation. Interventions: One hundred percent oxygen and iNO at 20 and 40 ppm were sequentially administered to the patients once they were optimized with IV vasodilators and inotropes. MEASUREMENTS AND MAIN RESULTS: Although no significant change was noted with oxygen, iNO 20 ppm reduced the mean pulmonary artery pressure (44.1 +/- 1.7 to 38.6 +/- 1.8 mmHg, p < 0.05), PVR index (823 +/- 47 to 621 +/- 55 dyne/s/m(2)/cm(5), p < 0.05), TPG (22.4 +/- 1.4 to 17.0 +/- 1.5 mmHg, p < 0.05), and right ventricular stroke work index (14.7 +/- 1.2 to 11.1 +/- 1.2 g . m/m(2)/beat, p < 0.05). In 13 of 21 patients, PVR decreased by greater than 25% after iNO therapy. Nine of these patients had PVR and TPG decrease to levels considered acceptable for OHT listing. CONCLUSIONS: iNO can further improve right ventricular hemodynamics even after presumed optimization with IV vasodilators and serves as a test of PVR reversibility during the preoperative assessment of OHT candidates.     

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.     

Diffusion tensor fractional anisotropy of the normal-appearing seven segments of the corpus callosum in healthy adults and relapsing-remitting multiple sclerosis patients

PURPOSE: To investigate the utility of whole-brain diffusion tensor imaging (DTI) in elucidating the pathogenesis of multiple sclerosis (MS) using the normal-appearing white matter (NAWM) of the corpus callosum (CC) as a marker of occult disease activity. MATERIALS AND METHODS: A high signal-to-noise ratio (SNR) and optimized entire brain DTI data were acquired in 26 clinically-definite relapsing and remitting multiple sclerosis (RRMS) patients and 32 age-matched healthy adult controls. The fractional anisotropy (FA) values of seven functionally distinct regions in the normal-appearing CC were compared between patients and controls. RESULTS: This study indicates that 1) there was a gender-independent FA heterogeneity of the functionally specialized CC segments in normal volunteers; 2) FA in the MS group was significantly decreased in the anterior (P=0.0039) and posterior (P=0.0018) midbody subdivisions of the CC, possibly due to a reduction of small-caliber axons; and 3) the FA of the genu of the CC was relatively intact in the MS patients compared to the healthy age-matched controls (P=0.644), while the splenium showed an insignificant trend of reduced FA values (P=0.248). The decrease in FA in any of the CC subdivisions did not correlate with disease duration (DD) or the expanded disability status scale (EDSS) score. CONCLUSION: The preliminary results are consistent with published histopathology and clinical studies on MS, but not with some published DTI reports. This study provides insights into the pathogenesis of MS, and the role played by compromised axonal integrity in this disease.     

Pharmacogenetic studies update in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.     

Involuntary emotional expression disorder (IEED) in Parkinson's disease

ObjectiveTo estimate the frequency and correlates of involuntary emotional expression disorder (IEED) in Parkinson's disease (PD) using the Center for Neurologic Study-Lability Scale (CNS-LS) and recently-proposed diagnostic criteria for IEED.BackgroundIEED is characterized by uncontrollable emotional episodes, typically unrelated to or in excess of the underlying mood, and occurring with minimal or no stimulus. IEED has been reported to occur in many neurological disorders and neurodegenerative diseases, but its prevalence and correlates in PD have not been well studied. Additionally, there is no published research using recently-proposed IEED diagnostic criteria in any population.Methods193 patients with idiopathic PD were assessed with a neuropsychiatric battery, including the CNS-LS and the 15-item Geriatric Depression Scale (GDS-15). A subset (N = 100) was also administered a diagnostic interview by a blinded rater that applied criteria for both IEED and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) depressive disorders.ResultsApplying formal diagnostic criteria, 7.0% of patients were diagnosed with IEED, and an additional 7.0% had subsyndromal IEED symptoms. Applying recommended CNS-LS cutoff scores from other populations, either 42.5% (cutoff ≥13) or 16.6% (cutoff ≥17) screened positive for IEED. Depressive symptoms were associated with higher CNS-LS scores (B[SE] = 0.27[.08], P = .001) but not with a diagnosis of IEED (odds ratio = 1.1, [95% CI = 1.0–1.3], P = .16). The CNS-LS had poor discriminant validity for an IEED diagnosis (AUC = .79, no cutoff value with sensitivity and specificity both >60%).ConclusionsIEED and depression are overlapping but distinct disorders in PD. IEED symptoms may occur in up to 15% of PD patients, but a disorder occurs in only half of those, suggesting that often IEED symptoms are not clinically significant in this population. The CNS-LS does not appear to be a good screening instrument for IEED in PD, in part due to its high correlation with depressive symptoms.     

Modulation of Physiological Responses as Indices of Attentional Bias in Dysphoria

The experimental results on attentional bias in depression have been contradictory. Research on physiological correlates that validate attentional bias have been scarce. The aim of the present study was to evaluate physiological responses associated with attentional bias in dysphoria. Heart rate and the galvanic skin response were recorded in 30 dysphoric individuals and 30 nondysphoric individuals while they performed an emotional Stroop task. Dysphoric individuals exhibited attentional bias and heart rate deceleration in response to unpleasant words. Nondysphoric individuals exhibited attentional bias toward pleasant words, accompanied by a higher skin conductance response. These results suggest that heart rate deceleration in response to unpleasant words correlated with attentional bias in dysphoric individuals.     

Venous thoracic outlet syndrome secondary to first rib osteochondroma in a pediatric patient

Osteochondromas account for 30% to 50% of benign osseous tumors and 10% of all bone tumors. Most of these lesions are found incidentally on imaging studies obtained for other reasons. Vascular compromise due to osteochondroma is a rare but well-recognized phenomenon and typically occurs in the lower extremity as a result of a tumor mass projecting into the popliteal fossa. We present the very rare case of a pediatric patient with venous thoracic outlet syndrome due to an osteochondroma of the first rib, and to our knowledge, this report is only the second such occurrence in the medical literature.