Citations

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and −0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects.

AbstractThe apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database—the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High‐order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor‐based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. Hum Brain Mapp 35:3903–3918, 2014. © 2014 Wiley Periodicals, Inc.

BackgroundHenoch‐Schönlein purpura (HSP) is a vasculitis that can affect the skin and kidneys. It is characterized by immunoglobulin (Ig) A‐predominant deposition in small blood vessels. To our knowledge, there has been no comparison of direct immunofluorescence (DIF) findings in skin and kidney biopsy specimens.MethodsWe retrospectively studied 21 adults with HSP who had IgA deposition in the skin and kidneys. The skin and kidney DIF findings were compared and tested for an association with the progression of renal disease.ResultsMean age of the patients was 51.4 years. Follow‐up data were available for 19 patients, of whom 5 had progression to chronic kidney disease or renal failure. Concordance between DIF findings on skin and renal biopsies was 100% for IgA, 80% for C3, 80% for IgG, 71% for IgM and 53% for fibrinogen. A worse renal outcome was associated with renal IgG deposition (p = 0.04). A trend for worse renal outcome was found with renal fibrinogen and skin IgM deposition (p = 0.10 and 0.14, respectively).ConclusionsIn this retrospective study of adult HSP, the concordance between DIF findings in skin and kidney specimens was low‐moderate. Further study is required to elucidate the mechanisms responsible for these differences in Ig deposition.

Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

ABSTRACTIntroduction: No study has correlated thermoregulatory sweat testing (TST) with histopathologic study of sweat glands (SGs) and SG nerve fibers (SGNFs). Methods: We studied 10 neuropathy patients in whom anhidrosis was found by TST and 10 matched controls. Skin biopsies were taken from both anhidrotic and sweating skin and immunohistochemical staining was done for nerves and basement membrane. For each biopsy, total tissue volume, total SG volume, and total SGNF length were measured. SGNF length per biopsy volume, SG volume per biopsy volume (SG%), and SGNF length per SG volume were calculated. Results: SGNF length per biopsy volume was reduced in anhidrotic site biopsies of patients compared with controls. SG% was decreased and SGNF length per SG volume increased in patients compared with controls. Conclusions: The results suggest a concomitant loss of SG volume and SGNF length in neuropathy, with greater loss of SGNFs in anhidrotic skin, possibly exceeding collateral reinnervation. Muscle Nerve 50: 528–534, 2014