Five Years' Experience with Tenon-Conjunctival Flaps in Phthisical Eyes.

BACKGROUND: To evaluate the efficacy of total Tenon-conjunctival flaps (TCFs) for coverage of phthisical eyes with normal corneal sensitivity. METHODS: A retrospective chart review was performed on 142 patients with mild monocular phthisis who underwent the TCF procedure to allow monocular scleral shell fitting at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. All patients had normal corneal sensation in their painless phthisical eye and were intolerant to cosmetic scleral shell fitting preoperatively. Consecutive patients over a five-year period were enrolled. Data were collected on functional success, duration of follow-up, and complications. The Tenon's and conjunctival layers were closed separately in 103 eyes and as a single layer in the remaining 39 eyes. Main outcome measures were functional success, defined as tolerance to the prosthetic scleral shell, and rate of postoperative complications such as wound retraction, epithelial cysts, and blepharoptosis. Fisher's exact test was used to analyze the association between the main outcome measures and type of flap closure. RESULTS: The mean duration of follow-up was 23.7±17.43 months. Functional success was achieved in 98.6% of eyes. Minor complications included epithelial inclusion cysts in 10 (7.04%) eyes and mild blepharoptosis in 9 (6.34%) eyes. Overall flap retraction was noted in 14 (9.86%) eyes. This complication occurred in 13 of 103 (33.3%) eyes with double layer closure and in 1 of 39 (0.97%) eyes with a single layer flap closure (p=0.11). CONCLUSIONS: TCF is an effective procedure to increase corneal thickness for coverage in phthisical eyes with positive corneal sensation. The incorporation of Tenon's capsule in the flap did not increase complications with a frequency similar to the classic Gundersen procedure.

Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese.

Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)). DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1(int/int) mice absorbed (64)Cu and (54)Mn from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of (59)Fe was virtually abolished in DMT1(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.

Quantification of thoracic blood flow using volumetric magnetic resonance imaging with radial velocity encoding: in vivo validation.

OBJECTIVES: The objective of this study was to validate radially undersampled 5-point velocity-encoded time-resolved flow-sensitive magnetic resonance imaging (MRI) ("PC-VIPR", phase contrast vastly undersampled imaging with isotropic resolution projection reconstruction magnetic resonance) for the quantification of ascending aortic (AAO) and main pulmonary artery (MPA) flow in vivo. MATERIALS AND METHODS: Data from 18 healthy volunteers (41.6 ± 16.2 years [range, 22-73 years]; body mass index, 26.0 ± 3.5 [19.1-31.4]) scanned at 3 T with a 32-channel coil were included. The left and right ventricular stroke volumes calculated from contiguous short-axis CINE-balanced steady state free precession (CINE-bSSFP) slices were used as the primary reference for cardiac output. Flow measured from 2-dimensional phase contrast MRI (2D-PC-MRI) in the AAO and the MPA served as the secondary reference. Time-resolved 4-dimensional flow-sensitive MRI (4D flow MRI) using PC-VIPR was performed with a velocity sensitivity of Venc = 150 cm/s reconstructed to 20 time frames at 1.4-mm isotropic spatial resolution. In 11 of 20 volunteers, phantom-corrected 4D flow MRI data were also assessed. Differences between methods of calculating the left ventricular and right ventricular cardiac output were assessed with the Bland-Altman analysis (BA, mean difference ±2SD). The QP/QS-ratio was calculated for each method. RESULTS: Initially, PC-VIPR compared unfavorably with CINE-bSSFP (left ventricular stroke volume: 96.5 ± 14.4 mL; right ventricular stroke volume: 93.6 ± 14.0 mL vs 81.2 ± 24.3 mL [AAO] and 85.6 ± 25.4 mL [MPA]; P = 0.027 and 0.25) with BA differences of -14.6 ± 44.0 mL (AAO) and -9.0 ± 45.9 mL (MPA). Whereas phantom correction had minor effects on 2D-PC-MRI results and comparison with CINE-bSSFP, it improved PC-VIPR results: BA differences between CINE-bSSFP and PC-VIPR after correction were -1.4 ± 15.3 mL (AAO) and -4.1 ± 16.1 mL (MPA); BA comparison with 2D-PC-MRI improved to -12.0 ± 48.1 mL (AAO) and -2.2 ± 19.5 mL (MPA). QP/QS-ratio results for all techniques were within physiologic limits. CONCLUSIONS: Accurate quantification of AAO and MPA flows with radially undersampled 4D flow MRI applying 5-point velocity encoding is achievable when phantom correction is used.

In vivo validation of 4D flow MRI for assessing the hemodynamics of portal hypertension.

PURPOSE: To implement and validate in vivo radial 4D flow MRI for quantification of blood flow in the hepatic arterial, portal venous, and splanchnic vasculature of healthy volunteers and patients with portal hypertension. MATERIALS AND METHODS: Seventeen patients with portal hypertension and seven subjects with no liver disease were included in this Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)-approved study. Exams were conducted at 3T using a 32-channel body coil with large volumetric coverage and 1.4 mm isotropic true spatial resolution. Using postprocessing software, cut-planes orthogonal to vessels were used to quantify flow (L/min) in the hepatic and splanchnic vasculature. RESULTS: Flow quantification was successful in all cases. Portal vein and supraceliac aorta flow demonstrated high variability among patients. Measurements were validated indirectly using internal consistency at three different locations within the portal vein (error = 4.2 ± 3.9%) and conservation of mass at the portal confluence (error = 5.9 ± 2.5%) and portal bifurcation (error = 5.8 ± 3.1%). CONCLUSION: This work demonstrates the feasibility of radial 4D flow MRI to quantify flow in the hepatic and splanchnic vasculature. Flow results agreed well with data reported in the literature, and conservation of mass provided indirect validation of flow quantification. Flow in patients with portal hypertensions demonstrated high variability, with patterns and magnitude consistent with the hyperdynamic state that commonly occurs in portal hypertension.

Four-dimensional, flow-sensitive magnetic resonance imaging of blood flow patterns in thoracic aortic dissections.

OBJECTIVE: The purpose of this study was to evaluate alterations in flow patterns in thoracic aortic dissections using 4-dimensional, flow-sensitive magnetic resonance imaging. METHODS: This prospective study was conducted at 2 academic tertiary referral medical centers. Thirteen 4-dimensional flow magnetic resonance imaging studies were performed in 12 subjects (4 female, aged 25-71 years) with thoracic aortic dissection using 3.0T clinical scanners. Qualitative assessment of flow patterns in the true and false lumina was performed in consensus by 3 cardiovascular radiologists. Quantitative analysis included measurement of net flow, retrograde flow, peak flow, and time-to-peak flow in the true and false lumina in the ascending aorta, aortic arch, and descending aorta. Differences in flow through the true and false lumina at each analysis plane were compared with the 2-tailed, paired Student t test. RESULTS: Flow patterns were significantly altered in association with different extents of disease, vessel dilatation, and post-therapeutic anatomy. Total flow per cardiac cycle and peak flow were higher in the true lumen than in the false lumen (P < .01). Retrograde flow was less in the true lumen than in the false lumen (P ≤ .01). Time-to-peak flow in the true lumen occurred later than in the false lumen (P = .05-.08). CONCLUSIONS: Four-dimensional, flow-sensitive magnetic resonance imaging at 3.0T provided qualitative and quantitative information on alterations of aortic flow in patients with thoracic aortic dissection. Future application of this magnetic resonance flow methodology may help provide insights into the pathophysiology and effects of flow alterations and establish prognostic indicators for the development of complications or aneurysm growth in patients with aortic dissection.

H(+)-coupled divalent metal-ion transporter-1: functional properties, physiological roles and therapeutics.

Divalent metal-ion transporter-1 (DMT1) is a widely expressed, iron-preferring membrane transport protein. Animal models establish that DMT1 plays indispensable roles in intestinal nonheme-iron absorption and iron acquisition by erythroid precursor cells. Rare mutations in human DMT1 result in severe microcytic-hypochromic anemia. When we express DMT1 in RNA-injected Xenopus oocytes, we observe rheogenic Fe(2+) transport that is driven by the proton electrochemical potential gradient. In that same preparation, DMT1 also transports cadmium and manganese but not copper. Whether manganese metabolism relies upon DMT1 remains unclear but DMT1 contributes to the effects of overexposure to cadmium and manganese in some tissues. There exist at least four DMT1 isoforms that arise from variant transcription of the SLC11A2 gene. Whereas these isoforms display identical functional properties, N- and C-terminal variations contain cues that direct the cell-specific targeting of DMT1 isoforms to discrete subcellular compartments (plasma membrane, endosomes, and lysosomes). An iron-responsive element (IRE) in the mRNA 3'-untranslated region permits the regulation of some isoforms by iron status, and additional mechanisms by which DMT1 is regulated are emerging. Natural-resistance-associated macrophage protein-1 (NRAMP1)-the only other member of the mammalian SLC11 gene family-contributes to antimicrobial function by extruding from the phagolysosome divalent metal ions (e.g. Mn(2+)) that may be essential cofactors for bacteria-derived enzymes or required for bacterial growth. The principal or only intestinal nonheme-iron transporter, DMT1 is a validated therapeutic target in hereditary hemochromatosis (HHC) and other iron-overload disorders.

4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot.

BACKGROUND: To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR). METHODS: CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test. RESULTS: 4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant. CONCLUSIONS: Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics.