In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion‐tracked slice‐to‐volume registration (MT‐SVR) method, we aimed to quantify tract‐specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2–8) diffusion scans of the fetal head (1–2 b = 0 s/mm² images and 12 diffusion‐sensitized images at b = 500 s/mm²). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT‐SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto‐occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract‐specific, GA‐related microstructural changes of the developing white matter in human fetal brain.     

CCL2/Monocyte Chemoattractant Protein-1 regulates inflammatory responses critical to healing myocardial infarcts

The CC chemokine Monocyte Chemoattractant Protein (MCP)-1/CCL2 has potent mononuclear cell chemo-attractant properties, modulates fibroblast and endothelial cell phenotype and may play an important role in wound healing. In order to examine whether MCP-1 critically regulates myocardial infarct healing, we studied the effects of MCP-1 gene disruption and antibody neutralization in a closed-chest model of reperfused murine myocardial infarction. MCP-1-/- mice had decreased and delayed macrophage infiltration in the healing infarct and demonstrated delayed replacement of injured cardiomyocytes with granulation tissue. In contrast, the time course and density of neutrophil infiltration was similar in MCP-1 null and wild-type animals. MCP-1-/- infarcts had decreased mRNA expression of the cytokines TNF-alpha, IL-1beta, TGF-beta2, -beta3, and IL-10 and demonstrated defective macrophage differentiation evidenced by decreased Osteopontin-1 expression. MCP-1 deficiency diminished myofibroblast accumulation but did not significantly affect infarct angiogenesis. Despite showing delayed phagocytotic removal of dead cardiomyocytes, MCP-1-/- mice had attenuated left ventricular remodeling, but similar infarct size when compared with wild-type animals. MCP-1 antibody inhibition resulted in defects comparable with the pathological findings noted in infarcted MCP-1-/- animals without an effect on macrophage recruitment. MCP-1 has important effects on macrophage recruitment and activation, cytokine synthesis and myofibroblast accumulation in healing infarcts. Absence of MCP-1 results in attenuated post-infarction left ventricular remodeling, at the expense of a prolonged inflammatory phase and delayed replacement of injured cardiomyocytes with granulation tissue.     

Evaluation of atypical human immunodeficiency virus immunoblot reactivity in blood donors

Blood donors reactive by enzyme-linked immunosorbent assay for antibody to the human immunodeficiency virus (HIV) who showed atypical patterns of viral core protein reactivity on Western blot were monitored for several months. Characterization of their antibodies was performed by 1) use of recombinant HIV proteins; 2) determination of cross-reactivity to HTLV-I, HTLV-II, and HTLV-IV: 3) assessment of immune status; and 4) identification of potentially interfering autoantibodies. Nineteen of 20 donors maintained the same HIV antibody reactivity throughout the follow-up period; the other donor became fully antibody-positive. Eighteen of 20 donors' sera showed clear reactivity with HIV recombinant core proteins. Ten of 19 donor samples demonstrated cross-reactivity to HTLV-IV; 3 of these 10 also cross-reacted with HTLV-I. The immune status of all donors was normal, although the medical histories and HLA antibody screens suggested possible autoimmune reactivity in 9 of 18 donors. During follow-up interviews, three donors reported possible risk factors for HIV infection that had not been acknowledged at the time of blood donation. We conclude that exclusion of donors with these atypical serologic test results is warranted while further studies to determine significance are being conducted.     

Progress in the diagnosis of deep venous thrombosis: the efficacy of real-time B-mode ultrasonic imaging

Seventy-six limbs with clinically suspected acute deep venous thrombosis (DVT) were evaluated by means of ultrasonic imaging (UI) to define the ability of this technique to detect acute and chronic venous obstruction and to determine the origin and distribution of venous thrombi. UI was compared with ascending contrast phlebography in 46 limbs and was found to be 100% accurate in detecting both acute and chronic venous thrombosis. Overall, acute DVT was present in 63 of 76 limbs (83%) studied. Acute DVT was found in 24% and recurrent acute DVT in 76%. Our results indicate that although the calf veins are the most common site of involvement (89%), thrombi may frequently arise simultaneously in multiple anatomic sites. All limbs with recurrent acute DVT had evidence of previous calf thrombi but only 13% had previous proximal disease. This suggests that asymptomatic calf DVT is common and the prevalence of recurrent acute DVT is significantly greater than previously believed. We found UI is a practical, accurate, non-invasive method for investigating the pathogenesis of venous disease.     

Use of ultrasonic venography in the evaluation of venous valve function

Forty healthy limbs and 31 limbs with suspected deep venous insufficiency were imaged with real-time B-mode ultrasound to determine valve location, anatomic characteristics, and function. Valve function was evaluated by comparison with Doppler ultrasonographic techniques, and the data clearly indicated that ultrasonic venography accurately localized and determined the extent of deep venous reflux. Ascending contrast venography was performed in 15 postphlebitic limbs for assessment of valve location. The results indicate that ultrasonic venography is a more accurate method for visualization of valves in this group of patients. Therefore, ultrasonographic imaging is a valuable technique for evaluating limbs with chronic venous insufficiency.     

Cultural Traditions as “Protective Factors” Among Latino Children of Illicit Drug Users

Family bonding was examined among Hispanic adolescents whose fathers are illicit drug users to ascertain whether such adolescents maintain close affective family ties or alienate themselves from their families given their father's use of illicit drugs and referral to a drug screening and treatment program. It was hypothesized that high levels of paternal drug use would be associated with the youth's alienation from the family. In addition, it was postulated that the adolescent's endorsement of traditional cultural values and social responsibility would protect her or him against this effect in relation to family bonding. These hypotheses are based on prior research that suggests that youth bonding to prosocial institutions, such as family, school, church, and community organizations, can be “protective” against drug use. More specifically, our analyses examined the role of level of acculturation in middle school, family traditionalism, American orientation, Latino orientation, and social responsibility in predicting adolescents' family bonding. Results indicated that the father's level of marijuana and/or methamphetamine use was unrelated to youth family bonding. Additionally, Latino and American cultural orientations and level of acculturation in middle school were not associated with family bonding. By contrast, social responsibility (the youth's citizenship and responsibility to the community) and family traditionalism (endorsing conservative cultural values regarding the maintenance of family traditions and respect for elders and family) were significantly associated with family bonding. In other words, among children of Latino illicit drug users, the youth's conservative family values and a responsible attitude toward community traditions were dual factors related to family bonding, perhaps operating also as sources of “protection” against youth problem behaviors.     

Quantitative tissue oxygen measurement in multiple organs using 19F MRI in a rat model

Measurement of individual organ tissue oxygen levels can provide information to help evaluate and optimize medical interventions in many areas including wound healing, resuscitation strategies, and cancer therapeutics. Echo planar ¹⁹F MRI has previously focused on tumor oxygen measurement at low oxygen levels (pO₂) <30 mmHg. It uses the linear relationship between spin‐lattice relaxation rate (R₁) of hexafluorobenzene (HFB) and pO₂. The feasibility of this technique for a wider range of pO₂values and individual organ tissue pO₂ measurement was investigated in a rat model. Spin‐lattice relaxation times (T₁= 1/R₁) of hexafluorobenzene were measured using ¹⁹F saturation recovery echo planar imaging. Initial in vitro studies validated the linear relationship between R₁ and pO₂ from 0 to 760 mmHg oxygen partial pressure at 25, 37, and 41°C at 7 Tesla for hexafluorobenzene. In vivo experiments measured rat tissue oxygen (ptO2) levels of brain, kidney, liver, gut, muscle, and skin during inhalation of both 30 and 100% oxygen. All organ ptO₂ values significantly increased with hyperoxia (P < 0.001). This study demonstrates that ¹⁹F MRI of hexafluorobenzene offers a feasible tool to measure regional ptO2 in vivo, and that hyperoxia significantly increases ptO2 of multiple organs in a rat model. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.