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1.  Spatial and temporal variability of Alexandrium cyst fluxes in the Gulf of Maine: Relationship to seasonal particle export and resuspension 
Quantification of Alexandrium cyst fluxes through the Gulf of Maine water column is central to understanding the linkage between the source and fate of annual Alexandrium blooms in the offshore waters. These blooms often lead to paralytic shellfish poisoning (PSP) and extensive closures of shellfish beds. We report here on time-series sediment trap deployments completed at four offshore locations in the gulf between 2005 and 2010 as components of two ECOHAB–GOM field programs. Data presented documents the substantial spatial and temporal fluctuations in Alexandrium fundyense cyst fluxes in the gulf. Cyst delivery out of the euphotic zone peaked primarily between July and August following annual spring–summer Alexandrium blooms and was greatest in the western gulf. At all sites, cyst flux maxima to the subsurface waters were rarely coincident with seasonal peaks in the total mass export of particulate material indicating that cyst delivery was primarily via individually sinking cysts. Where persistent benthic nepheloid layers (BNLs) exist, significant sediment resuspension input of cysts to the near-bottom water column was evidenced by deep cyst fluxes that were up to several orders of magnitude greater than that measured above the BNL. The largest cyst fluxes in the BNL were observed in the eastern gulf, suggesting greater resuspension energy and BNL cyst inventories in this region. Temporal similarities between peak cyst export out of the upper ocean and peak cyst fluxes in the BNL were observed and document the contribution of seasonal, newly formed cysts to the BNL. The data however also suggest that many Alexandrium cells comprising the massive, short-lived blooms do not transition into cysts. Time-series flow measurements and a simple 1D model demonstrate that the BNL cyst fluxes reflect the combined effects of tidal energy-maintained resuspension, deposition, and input of cysts from the overlying water column.
doi:10.1016/j.dsr2.2012.11.001
PMCID: PMC4243940  PMID: 25431527
Gulf of Maine; Particulate flux; Sediment traps; Alexandrium; Cysts; Resuspension
2.  Benthic nepheloid layers in the Gulf of Maine and Alexandrium cyst inventories 
Cysts residing in benthic nepheloid layers (BNLs) documented in the Gulf of Maine have been proposed as a possible source of inoculum for annual blooms of a toxic dinoflagellate in the region. Herein we present a spatially extensive data set of the distribution and thickness of benthic nepheloid layers in the Gulf of Maine and the abundance and inventories of suspended Alexandrium fundyense cysts within these near-bottom layers. BNLs are pervasive throughout the gulf and adjacent Bay of Fundy with maximum layer thicknesses of 50–60 m observed. Mean BNL thickness is 30 m in the eastern gulf and Bay of Fundy, and 20 m in the western gulf. Cyst densities in the near-bottom particle resuspension layers varied by three orders of magnitude across the gulf with maxima of 105 cysts m−3. An important interconnection of elevated BNL cyst densities is observed between the Bay of Fundy, the Maine Coastal Current and the south-central region of the gulf. BNL cyst inventories estimated for the eastern and western gulf are each on the order of 1015 cysts, whereas the BNL inventory in the Bay of Fundy is on the order of 1016 . Although BNL cyst inventories in the eastern and western gulf are 1–2 orders of magnitude smaller than the abundance of cysts in the upper 1 cm of sediment in those regions, BNL and sediment-bound cyst inventories are comparable in the Bay of Fundy. The existence of widespread BNLs containing substantial cyst inventories indicates that these near-bottom layers represent an important source of germinating A. fundyense cysts in the region.
doi:10.1016/j.dsr2.2013.05.021
PMCID: PMC4238928  PMID: 25419055
Benthic nepheloid layer; Suspended particulate matter; Gulf of Maine; Alexandrium fundyense; Cysts
3.  Disease control using low-dose-rate brachytherapy is unaffected by comorbid severity in oral cancer patients 
The British Journal of Radiology  2011;84(1006):930-938.
Objective
The aim of this study was to evaluate the outcome and complications of low-dose-rate brachytherapy (LDR-BT) for oral cancer according to comorbidity.
Methods
The records of a total of 180 patients who received LDR-BT for T1-2N0M0 oral cancers between January 2005 and December 2007 were analysed. The comorbidities of the patients were retrospectively graded according to the Adult Comorbidity Evaluation-27, and the relationships between the comorbidity grades and survival, disease control and the incidence of complications were analysed.
Results
The 2 year overall survival rates of patients with no comorbidity, Grade 1, Grade 2 and Grade 3 comorbidity were 87%, 85%, 76% and 65%, respectively, and the reduction in the survival rate according to comorbid severity was significant in a univariate analysis (p = 0.032) but not in a multivariate analysis including other clinical factors. Cause-specific survival, locoregional control and local control were not related to the comorbidity grade, or any other clinical factors. Grade 2 or 3 complications developed in 27% of the patients. The incidence of complications was unrelated to the comorbidity grade.
Conclusion
The disease control of oral cancer and the incidence of complications after LDR-BT were not related to comorbid severity. LDR-BT is a useful and safe treatment for patients regardless of the presence of severe comorbidity.
doi:10.1259/bjr/53223221
PMCID: PMC3473764  PMID: 21224307
4.  Brachytherapy for tongue cancer in the very elderly is an alternative to external beam radiation 
The British Journal of Radiology  2011;84(1004):747-749.
Background
The result of curative treatment for very elderly patients with tongue carcinoma has not been reported to date. We retrospectively reviewed the results of brachytherapy in 125 the patients aged over 75 years.
Methods
The results of brachytherapy in 125 patients, 75 years old or older, with Stage I or II squamous cell carcinoma of the oral tongue were reviewed. The 125 cases consisted of 31 Stage I and 94 Stage II cases; 67 patients were under 80 years old and 58 were over 80 years old. All patients were treated using low-dose-rate brachytherapy (198Au/222Rn: 59 cases; 192Ir: 38 cases; 226Ra/137Cs: 28 cases).
Results
None of the patients stopped treatment during the course of brachytherapy. The 3 year and 5 year control rates of the primary lesions were both 86%. Post-brachytherapy neck node metastasis was diagnosed in 43 cases and radical neck dissection was performed for 24 cases (21 of the 24 cases were under 80 years old). As a result, the 7 year disease-specific survival (DSS) rate for patients aged under 80 years old was 70% and 41% for those over 80 years old (p = 0.03).
Conclusion
The brachytherapy for elderly patients with tongue cancer was safe, and the control of the primary lesion was almost the same as in younger patients. However, modalities available to treat neck node metastasis are limited. More conservative surgical approaches combined with post-operative irradiation may be advocated for neck node metastasis for elderly patients with tongue cancer.
doi:10.1259/bjr/23130739
PMCID: PMC3473442  PMID: 20682593
5.  Origin of the relatively low transport mobility of graphene grown through chemical vapor deposition 
Scientific Reports  2012;2:337.
The reasons for the relatively low transport mobility of graphene grown through chemical vapor deposition (CVD-G), which include point defect, surface contamination, and line defect, were analyzed in the current study. A series of control experiments demonstrated that the determinant factor for the low transport mobility of CVD-G did not arise from point defects or surface contaminations, but stemmed from line defects induced by grain boundaries. Electron microscopies characterized the presence of grain boundaries and indicated the polycrystalline nature of the CVD-G. Field-effect transistors based on CVD-G without the grain boundary obtained a transport mobility comparative to that of Kish graphene, which directly indicated the detrimental effect of grain boundaries. The effect of grain boundary on transport mobility was qualitatively explained using a potential barrier model. Furthermore, the conduction mechanism of CVD-G was also investigated using the temperature dependence measurements. This study can help understand the intrinsic transport features of CVD-G.
doi:10.1038/srep00337
PMCID: PMC3313616  PMID: 22468224
6.  In-the-bag scleral suturing of intraocular lens in eyes with severe zonular dehiscence 
Eye  2011;26(1):88-95.
Purpose
To compare the degree of tilt and decentration of an intraocular lens (IOL), refractive status, and prediction error between eyes that underwent trans-scleral suturing of the IOL within the capsular bag (in-the-bag scleral suturing) and eyes that underwent scleral suturing outside of the bag (out-of-the-bag scleral suturing) because of severe zonular dehiscence.
Patients and methods
Thirty eyes that underwent in-the-bag scleral suturing of an IOL and 38 eyes that underwent out-of-the-bag scleral suturing were recruited sequentially. The tilt and decentration of the IOL, anterior chamber depth, manifest refractive spherical equivalent (MRSE), prediction error, and incidence of complications were examined.
Results
The mean tilt angle and the decentration length of the IOL of the in-the-bag suturing group were significantly less than those of the out-of-the-bag suturing group (P=0.0003 in tilt and P=0.0391 in decentration), although the anterior chamber depth was similar. The mean MRSE and prediction error of the in-the-bag suturing group were less than those of the out-of-the-bag suturing group (P=0.0006 in MRSE and P=0.0034 in error). The incidence of vitreous loss was less in the in-the-bag suturing group than in the out-of-the-bag suturing group (20% vs63.2%, P=0.0009).
Conclusions
The tilt and decentration of the IOL after in-the-bag scleral suturing are significantly less than those after out-of-the-bag scleral suturing, which may lead to less MRSE and less prediction error. As the incidence of vitreous loss is less after in-the-bag scleral suturing, in-the-bag suturing is advantageous for eyes of younger patients and of less complicated cases.
doi:10.1038/eye.2011.242
PMCID: PMC3259581  PMID: 21941359
cataract surgery; scleral suture fixation of intraocular lens; zonular dehiscence; intraocular lens displacement; refractive prediction error
7.  FDDNP Binding Using MR Derived Cortical Surface Maps 
NeuroImage  2009;49(1):240-248.
Objectives
To assess quantitatively the cortical pattern profile of regional FDDNP binding to beta-amyloid and neurofibrillary tangles on MR derived cortical maps, FDDNP PET images were corrected for movement and partial volume (PV), and optimized for kernel size. 3
Methods
FDDNP DVR PET images from 23 subjects (7 with Alzheimer’s disease (AD), 6 with mild cognitive impairment and 10 controls) were obtained from Logan analysis using cerebellum as reference. A hemispheric cortical surface model for each subject was extracted from the MRI. The same transformations were applied to the FDDNP DVR PET images to map them into the same space. The cortical map with PV correction was calculated as the ratio of the DVR cortical surface and that of the simulated map, created from the mask derived from MRI and smoothed to the PET resolution. Discriminant analysis was used to order the FDDNP DVR cortical surfaces based on subjects’ disease state. Linear regression was used to assess the rate of change of DVR vs. MMSE for each hemispheric cortical surface point.
Results
The FDDNP DVR cortical surface corrected for movement and PV had less hemispheric asymmetry. Optimal kernel size was determined to be 9mm. The corrected cortical surface map of FDDNP DVR showed clear spatial pattern that was consistent with the known pathological progression of AD.
Conclusion
Correcting for movement, PV as well as optimizing kernel size provide sensitive statistical analysis of FDDNP distribution which confirms in the living brain known pathology patterns earlier observed with cognitive decline with brain specimens.
doi:10.1016/j.neuroimage.2009.08.035
PMCID: PMC2764817  PMID: 19703569
cortical surface maps; MR; FDDNP PET
8.  Cri-du-Chat Syndrome Cytogenetically Cryptic Recombination Aneusomy of Chromosome 5: Implications in Recurrence Risk Estimation 
Molecular Syndromology  2010;1(2):95-98.
Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry. Most cri-du-chat syndrome cases result from a sporadic de novo deletion that is associated with a low recurrence risk. On rare occasions, however, cri-du-chat syndrome with 5p monosomy can be accompanied by 5q trisomy. This combination is virtually always associated with parental large pericentric inversions. Among previously reported cri-du-chat syndrome cases with 5p monosomy accompanied by 5q trisomy, the aneusomy of chromosome 5 in all but one case was cytogenetically visible using G-banding. When an accompanying 5q trisomy is detected, a significant recurrence risk is expected. We here report on a patient with cri-du-chat syndrome phenotype who initially exhibited a normal karyotype on G-banding but in whom molecular analysis using multiplex ligation-dependent probe amplification and array comparative genomic hybridization revealed a 5p deletion accompanied by a 5q duplication. Parental chromosomal testing led to the identification of a very large pericentric inversion, of which breakpoints resided at the terminal regions of 5p15.31 and 5q35.1. This information was vital for counseling the family regarding the significantly high recurrence risk.
doi:10.1159/000319321
PMCID: PMC2941846  PMID: 21045963
Genetic counseling; Monosomy 5p; Trisomy 5q
9.  Three-dimensional preoperative maps of hippocampal atrophy predict surgical outcomes in temporal lobe epilepsy 
Neurology  2005;65(7):1094-1097.
The authors used surface-based anatomic mapping to detect features of hippocampal anatomy that correlated with surgical outcomes in patients undergoing surgery for mesial temporal lobe epilepsy with hippocampal sclerosis. Compared with a seizure-free group, hippocampal profiles for the non–seizure-free group had greater diffuse ipsilateral atrophy and more region-specific contralateral atrophy in the anterior, lateral hippocampus. These atrophic regions may indicate areas of increased epileptogenicity, contributing to poorer surgical outcomes.
doi:10.1212/01.wnl.0000179003.95838.71
PMCID: PMC2770433  PMID: 16217065
10.  Reactive lymphoid hyperplasia of the liver in a patient with multiple carcinomas: a case report and brief review 
Journal of Clinical Pathology  2006;59(9):990-992.
A rare case of reactive lymphoid hyperplasia (RLH) of the liver in a 75‐year‐old woman admitted to hospital for surgical treatment of gastric, caecal and colon carcinomas is described here. Two nodular lesions in the left and right lobes of the liver were clinically diagnosed as metastatic tumours by computed tomography of the abdomen. A demarcating grey–white mass of size 1.4 cm was observed in a partially resected liver specimen. On examining the lesion microscopically, it was found to be composed of hyperplastic lymphoid follicles, lymphocytes, plasma cells, other inflammatory cells and interlaced hyalinised fibrous tissues. In the portal tracts around the lesion, chronic inflammatory cell infiltrates were seen, but no interface hepatitis or lymphoid follicle was observed. No evidence of monoclonality was observed by immunohistochemistry for B and T cell markers, in situ hybridisation for κ and λ light chains, and polymerase chain reaction analysis of immunoglobulin heavy chains or T cell receptor β and γ gene rearrangements. Bcl‐2 immunoreactivity was not observed in the germinal centre. Epstein–Barr virus (EBV) antigen (latent membrane protein‐1) and EBV‐encoded small RNAs were not detected. A proliferation neither of myofibroblasts nor of cells positive for follicular dendritic cell markers was observed. RLH, formerly known as pseudolymphoma, has been reported of the liver in only 14 cases and is considered to be a differential diagnosis of small nodular lesions of the liver. That RLH has an inflammatory reactive nature, not a neoplastic disposition, and that EBV does not participate in the pathogenesis of RLH is supported by this case.
doi:10.1136/jcp.2005.028886
PMCID: PMC1860472  PMID: 16935975
11.  Visual function in patients with yellow tinted intraocular lenses compared with vision in patients with non‐tinted intraocular lenses 
The British Journal of Ophthalmology  2006;90(8):1019-1023.
Aim
To compare the visual function in patients with short wavelength blue light blocking yellow tinted intraocular lenses (IOLs) with that in patients with non‐tinted IOLs.
Methods
74 patients scheduled for bilateral cataract surgery underwent implantation of either yellow IOLs (HOYA YA60BB) or non‐tinted IOLs (VA60BB) in both eyes. Contrast visual acuity with and without a glare source was measured under photopic (100 cd/m2) and mesopic (slightly higher luminance than typically used—5 cd/m2) conditions at 2 weeks and 3 months after surgery using the contrast sensitivity accurate tester. Visual acuity and the incidence of patients who noted cyanopsia were also examined.
Results
No significant differences between the yellow tinted and non‐tinted IOL groups were observed in mean visual acuity or in photopic or higher luminance mesopic contrast visual acuity with and without glare source at either 2 weeks or 3 months after surgery. Furthermore, there was no significant difference in contrast visual acuity loss as a result of glare. The incidence of patients who noticed cyanopsia was significantly less in the yellow tinted IOL group than in the non‐tinted IOL group at 2 weeks after surgery (p = 0.0234), but no patients reported cyanopsia at 3 months.
Conclusion
Visual function in patients with yellow tinted IOLs is virtually the same as that in patients with non‐tinted IOLs.
doi:10.1136/bjo.2006.090712
PMCID: PMC1857188  PMID: 16597662
yellow tinted intraocular lens; contrast sensitivity; glare disability; cyanopsia
12.  Functional outcome in patients with osteosarcoma around the knee joint treated by minimised surgery 
International Orthopaedics  2007;32(1):63-68.
The functional results of prostheses and osteoarticular grafts for osteosarcoma around the knee joint are not satisfactory because of poor durability and gross distortion of the normal anatomy. We have investigated the functional outcome of intentional marginal excision for osteosarcoma around the knee joint in conjunction with caffeine-potentiated chemotherapy. Twenty-one patients with AJCC stage IIB high-grade osteosarcoma around the knee joint were given three to five preoperative courses of intra-arterial cisplatin and caffeine with or without doxorubicin. The histological response in these 21 patients to preoperative chemotherapy was grade IV (no viable cells) in 19 patients and grade III (only scattered foci of viable cells) in 2. The patients were separated into three groups on the basis of patterns of tumour excision. The first group underwent marginal excision of the proximal fibula, the second underwent epiphysis preservation followed by distraction osteogenesis, and the third underwent joint resection and reconstruction. The mean functional evaluations were 100, 95, and 88%, respectively. No local tumour recurrence was seen at mean follow-up of 97 months. Marginal excision of the proximal fibula resulted in excellent function. Preservation of the epiphysis leads to better function than joint resection.
doi:10.1007/s00264-006-0289-2
PMCID: PMC2219930  PMID: 18214479
13.  Elevation of a collagenase generated type II collagen neoepitope and proteoglycan epitopes in synovial fluid following induction of joint instability in the dog 
Summary
Clinical relevance
Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations.
Objective
The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA.
Design
A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55 ± 1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(–) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed.
Results
Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(–) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture.
Conclusions
Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(–) epitope in synovial fluid were significantly increased by 4 weeks and remained elevated for at least 16 weeks after CCL rupture. This suggests that in dogs the COL2-3/4C long neoepitope and 3B3(–) epitope are sensitive markers for changes in joint cartilage turnover in joints that are developing OA.
doi:10.1053/joca.2002.0812
PMCID: PMC2048684  PMID: 12479389
COL2-3/4 long, 3B3(—); osteoarthritis; monopolar radiofrequency energy; knee; canine; cranial cruciate ligament
14.  Posterior capsule opacification after implantation of a hydrogel intraocular lens 
Aim: To compare the degree of posterior capsule opacification (PCO) in eyes with a hydrophilic hydrogel intraocular lens (IOL) with that in eyes with a hydrophobic acrylic IOL.
Methods: Ninety five patients underwent a hydrogel IOL implantation in one eye and an acrylic IOL implantation in the opposite eye. The PCO value of these patients was measured using the Scheimpflug videophotography system at 1, 6, 12, 18, and 24 months postoperatively. The rate of neodymium:YAG (Nd:YAG) laser posterior capsulotomy and visual acuity were also evaluated.
Results: The mean PCO value in the hydrogel group increased significantly (p<0.0001), while that in the acrylic group did not show significant change. The PCO value in the hydrogel group was significantly greater than that in the acrylic group throughout the follow up period. Kaplan-Meier survival analysis determined that the Nd:YAG capsulotomy rate in the hydrogel group was significantly higher than that in the acrylic group (p<0.0001). Mean visual acuity in the hydrogel group decreased significantly with time (p<0.0001), and became significantly worse than that in the acrylic group at 18 and 24 months postoperatively.
Conclusion: Posterior capsule opacification in eyes with a hydrophilic hydrogel IOL is significantly more extensive than that in eyes with a hydrophobic acrylic IOL, and results in a significant impairment of visual acuity.
doi:10.1136/bjo.2003.023580
PMCID: PMC1771981  PMID: 14736768
acrylic intraocular lens; hydrogel intraocular lens; neodymium:YAG capsulotomy; posterior capsule opacification
15.  Dissecting Aneurysm of the Vertebral Artery Developed after Microvascular Decompression for Hemifacial Spasm 
Interventional Neuroradiology  2006;12(Suppl 1):145-147.
Summary
We report a rare case of a ruptured de novo dissecting aneurysm induced by ethyl 2-cyano-acrylate. A 39-year-old woman underwent microvascular decompression for left hemifacial spasm. The offending vessel was left posterior inferior cerebellar artery (PICA). Left vertebral artery (VA) was mobilized and affixed to the dura mater with cyanoacrylate to remove pressure of PICA to the root exit zone of the facial nerve. The left VA was found to be intact at the time of the operation.
One year later, the patient sufferd subarachnoid haemorrhage (SAH) caused by rupture of a newly-developed dissecting aneurysm of the left VA. Endovascular occlusion of the dissecting site was performed using Guglielmi detachable coils. We suppose mechanical injury and chemical reaction of ethyl 2-cyanoacrylate induced dissecting aneurysm.
PMCID: PMC3387942  PMID: 20569620
cyanoacrylate, microvascular decompression, cerebral aneurysm
16.  The Stenting to Internal Carotid Artery Stenosis (ICS) in Petrous Portion 
Interventional Neuroradiology  2006;12(Suppl 1):193-196.
Summary
In the safety stenting, it is important to get to know the characteristics of a plaque. In petrous carotid artery stenosis, it is difficult to know the characteristics of the plaque. We paid our attention to the MPRAGE (Magnetization Prepared Rapid Acquisition with Gradient Echo) method on high resolving power MRI.
By the MPRAGE method, low intensity was observed in these lesions of all cases. This result suggested that the plaque in petrous portion was a fibrous plaque. This method is useful to get to know the characteristics of a plaque in petrous portion before endovascular treatment.
PMCID: PMC3387951  PMID: 20569630
Petrous carotid stenosis, plaque characterization, MPRAGE
17.  Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity 
The British Journal of Ophthalmology  2003;87(10):1291-1295.
Aims: To search for mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) and to delineate the defective gene associated clinical features.
Methods: Direct sequencing following polymerase chain reaction of exons of FZD4 was performed for 24 probands with FEVR (18 familial and six sporadic), and some of their families. Clinical symptoms among individuals with mutations were assessed.
Results: Four novel mutations were identified in four patients with familial and one with sporadic FEVR. Three of these mutations were missense (M105V, R417Q, and G488D) and one was a nonsense change (W319X). M105V, R417Q, and G488D co-segregated with the disease. None of these sequence changes was found among 300 chromosomes from 150 healthy volunteers. The severity of vitreoretinopathy in the individuals involved in this study varied, but no patient with mutations in FZD4 exhibited rhegmatogenous retinal detachment although this pathology is thought to be the most common type of retinal detachment in FEVR.
Conclusion: FZD4 gene mutations were found in some cases of autosomal dominant and sporadic FEVR. FZD4 mutations were responsible for FEVR with variable clinical manifestations.
PMCID: PMC1920788  PMID: 14507768
gene mutations; retinal detachment; familial exudative vitreoretinopathy
18.  QT dispersion and left ventricular morphology in patients with hypertrophic cardiomyopathy 
Heart  2003;89(8):882-886.
Objective: To evaluate the relation between QT variables and disproportion of left ventricular wall hypertrophy in patients with hypertrophic cardiomyopathy.
Design: Retrospective analysis of the results of echocardiography and electrocardiography.
Setting: University hospital (tertiary referral centre).
Patients: 70 patients with hypertrophic cardiomyopathy were divided into four groups according to the distribution of left ventricular wall hypertrophy on cross sectional echocardiography: group A—hypertrophy confined to the interventricular septum; group B—hypertrophy confined to the interventricular septum and left ventricular anterior wall; group C—hypertrophy confined to the interventricular septum, left ventricular anterior wall, and lateral free wall; group D—hypertrophy involving all portions of the left ventricle.
Main outcome measures: QT intervals and QT dispersion in precordial six lead ECGs.
Results: There were no significant differences in the maximum left ventricular wall thickness among the four groups, and maximum and minimum QTc intervals also did not differ. QTc dispersion was increased significantly in groups A and B compared with groups C and D. Dispersions of the interval from the J point to the end of the T wave (JTc dispersions) in groups A and B were also increased significantly compared with groups C and D. By linear regression analysis, QTc and JTc dispersions correlated with the ratio of the interventricular septal thickness to left ventricular posterior wall thickness (p = 0.0152 and p = 0.0075, respectively).
Conclusions: QT dispersion may be affected by not only electrical inhomogeneity but also by morphological inhomogeneity of the left ventricle in patients with hypertrophic cardiomyopathy.
PMCID: PMC1767760  PMID: 12860864
hypertrophic cardiomyopathy; left ventricular morphology; QT dispersion
19.  Frequency of ciliary body or retinal breaks and retinal detachment in eyes with atopic cataract 
Aim: To determine the frequency of ciliary body or retinal breaks and retinal detachment in eyes with atopic cataract.
Methods: The records of 106 eyes (74 patients) with atopic cataract that underwent cataract extraction were reviewed. The frequency of ciliary body or retinal breaks and retinal detachment was classified by their presence preoperatively and postoperatively, and by cataract type.
Results: Breaks were detected preoperatively in 27 eyes (25.5%) of 17 patients in the ciliary body (20 eyes, 18.9%), near the ora serrata (five eyes, 4.7%), and in undefined locations (two eyes, 1.9%). Among these, 16 eyes (15.1%) had already developed retinal detachment. After surgery, a ciliary body break occurred in one eye (0.9%) and retinal detachment in four eyes (3.8%) of three patients. The breaks that caused postoperative retinal detachment were in the ciliary body. When classified by cataract type, the highest frequency of breaks was associated with mature cataracts (35.0%), and all eyes with breaks developed retinal detachment.
Conclusions: One fourth of eyes with atopic cataract had breaks in the ciliary body or ora serrata, or retinal detachment preoperatively. The highest frequency of either breaks or retinal detachment was associated with mature cataract. The frequency of breaks or detachment that occurred postoperatively (approximately 5%) was lower than that present preoperatively.
PMCID: PMC1771221  PMID: 12140212
ciliary body breaks; retinal breaks; retinal detachment; atopic cataract
20.  Antimicrobial Activity of Murine Lung Cells against Staphylococcus aureus Is Increased In Vitro and In Vivo after Elafin Gene Transfer  
Infection and Immunity  2005;73(6):3609-3617.
Staphylococcus aureus is a pathogen often found in pneumonia and sepsis. In the context of the resistance of this organism to conventional antibiotics, an understanding of the regulation of natural endogenous antimicrobial molecules is of paramount importance. Previous studies have shown that both human and mouse airways express a variety of these molecules, including defensins, cathelicidins, and the four-disulfide core protein secretory leukocyte protease inhibitor. We demonstrate here by culturing mouse tracheal epithelial cells at an air-liquid interface that, despite the production of Defb1, Defb14, and Defr1 in this system, these cells are unable to clear S. aureus when exposed to this respiratory pathogen. Using an adenovirus (Ad)-mediated gene transfer strategy, we show that overexpression of elafin, an anti-elastase/antimicrobial molecule (also a member of the four-disulfide core protein family), dramatically improves the clearance of S. aureus. In addition, we also demonstrate that this overexpression is efficient in vivo and that intratracheal instillation of Ad-elafin significantly reduced the lung bacterial load and demonstrates concomitant anti-inflammatory activity by reducing neutrophil numbers and markers of lung inflammation, such as bronchoalveolar lavage levels of tumor necrosis factor and myeloperoxidase. These findings show that an increased antimicrobial activity phenotype is provided by the elafin molecule and have implications for its use in S. aureus-associated local and systemic infections.
doi:10.1128/IAI.73.6.3609-3617.2005
PMCID: PMC1111862  PMID: 15908390
21.  Strategy for Prevention of Restenosis after PTA 
Interventional Neuroradiology  2008;10(Suppl 1):63-66.
Summary
Percutaneous transluminal angioplasty (PTA) has been a useful therapy to treat stenosis of cervical internal carotid artery (ICA) or vertebral artery (VA). Here we show that our clinical results regarding preventive effect of stenting on restenosis after PTA in the ICA and VA origin. We also show our experimental studies with gene transfer techniques aiming reduction of restenosis after balloon-injury in rat carotid artery. It has been reported that drug-eluting stent inhibits restenosis after coronary angioplasty. Further understanding of the mechanism of restenosis and application of these new modalities may lead to better clinical results in angioplasty of the craniocervical arteries.
PMCID: PMC3490176  PMID: 20587274
22.  Anterior capsule contraction and intraocular lens decentration and tilt after hydrogel lens implantation 
The British Journal of Ophthalmology  2001;85(11):1294-1297.
AIM—To prospectively investigate changes in the area of the anterior capsule opening, and intraocular lens (IOL) decentration and tilt after implantation of a hydrogel IOL.
METHODS—100 patients underwent implantation of a hydrogel IOL in one eye and an acrylic IOL implantation in the opposite eye. The area of the anterior capsule opening, and the degree of IOL decentration and tilt were measured using the Scheimpflug videophotography system at 3 days, and at 1, 3, and 6 months postoperatively.
RESULTS—The mean anterior capsule opening area decreased significantly in both groups. At 6 months postoperatively, the area in the hydrogel group was significantly smaller than that in the acrylic group. The mean percentage of the area reduction in the hydrogel group was also significantly greater than that in the acrylic group, being 16.9% in the hydrogel group and 8.8% in the acrylic group. In contrast, IOL decentration and tilt did not progress in either group. No significant differences were found in the degree of IOL decentration and tilt throughout the follow up period.
CONCLUSIONS—Contraction of the anterior capsule opening was more extensive with the hydrogel IOL than with the acrylic IOL, but the degree of IOL decentration and tilt were similar for the two types of lenses studied.


doi:10.1136/bjo.85.11.1294
PMCID: PMC1723752  PMID: 11673291
23.  Interferon responsiveness in patients infected with hepatitis C virus 1b differs depending on viral subtype 
Gut  2001;49(2):263-267.
BACKGROUND—Genotype 1b of hepatitis C virus (HCV) comprises mainly three subtypes, each named for its geographic prevalence (worldwide, W; Japan, J; and not in Japan, NJ).
AIM—To characterise the newly identified subtypes of genotype 1b and to review factors associated with response to interferon (IFN) for each subtype.
PATIENTS—Chronic hepatitis patients (80 men and 41 women; mean age 48.5 years, range 20.7-69.3) with HCV genotype 1b (W type, n=41; J type, n=38) or genotype 2a (n=42) were treated according to the same IFN protocol. Forty four patients (36.4%) negative for serum HCV RNA six months after cessation of treatment were considered complete responders.
METHODS—Factors associated with complete response were investigated.
RESULTS—Genotype 2a patients had lower viral loads (odds ratio 0.11 (95% confidence intervals (CI) 0.049-0.256)) and a better IFN response (odds ratio 0.25 (95% CI 0.117-0.552)) than genotype 1b patients whereas W type and J type patients had similar viral loads and responses to IFN. IFN response in W type patients was associated with female sex (odds ratio 0.23 (95% CI 0.055-0.983)) and low viral load (odds ratio 84.00 (95% CI 14.04-502.6)) whereas response in J type patients was related to transfusion history (odds ratio 7.20 (95% CI 1.443-35.91)), low viral load (odds ratio 117.0 (95% CI 17.82-768.3)), and genetic mutation in the interferon sensitivity determining region of the virus (odds ratio 0.08 (95% CI 0.013-0.553)). Multivariate analysis found low viral load (odds ratio 64.19 (95% CI 14.66-281.06)) to be the only significant independent factor associated with IFN response.
CONCLUSIONS—Factors associated with IFN responsiveness in HCV infection differ with viral subtype.


Keywords: hepatitis C virus; genotype 1b; chronic hepatitis; interferon therapy; interferon sensitivity determining region
doi:10.1136/gut.49.2.263
PMCID: PMC1728417  PMID: 11454804
24.  Staged Carotid Stenting and Carotid Endarterectomy for Bilateral Internal Carotid Artery Stenosis 
Interventional Neuroradiology  2004;9(Suppl 1):143-148.
Summary
The purpose of this study was to evaluate the efficacy and safety of staged carotid stenting (CS) and carotid endarterectomy (CEA) for bilateral internal carotid artery stenosis.
With this strategy, initial carotid stenting was performed for the high grade carotid stenosis to reduce the risk of subsequent CEA. Eight patients were treated with staged CS and CEA; CS for asymptomatic side followed by CEA for symptomatic side. Sufficient revascularization was obtained in all procedures but one CS procedure.
Two minor stroke caused by distal embolism occurred during the perioperative period of CS. Postprocedural persistent hypotension was observed in one CS procedure. The mean interval between CS and CEA was 19.8 days. In conclusion, although our strategy has some advantages such as avoidance of bilateral cranial nerve palsy and shorter admission period over staged CEA, relatively high complication rate was noted at the first CS without any stroke morbidity post CEA.
Our preliminary result showed that further reduction of periprocedural complication rate at the initial stenting is mandatory for this approach justified.
PMCID: PMC3553470  PMID: 20591244
bilateral internal carotid artery stenosis, carotid stenting, carotid endarterectomy
25.  Local Thrombolysis for Acute Ischemic Stroke Based on Findings of Diffusion and Perfusion MRI  
Interventional Neuroradiology  2002;7(Suppl 1):193-196.
Summary
Cerebral per fusion and cerebral tissue integrity were studied in 13 patients with acute embolic stroke in the territory of the internal carotid artery by diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) within six hours after onset. PWI/DWI mismatch lesion was depicted in six patients. MCA was occluded in five of six patients, who underwent local thrombolytic therapy. In three cases, complete restoration of the cerebral circulation was obtained and enlargement of irreversible brain damage compared to initial DWI lesion was prevented. Seven patients without PWI/DWI mismatch did not undergo thrombolytic therapy. Spontaneous reopening of occluded MCA was verified with subsequent cerebral angiography in one ofseven patients. CT depicted symptomatic intracerebral hemorrhage in this patient. It is concluded that DWI and PWI in combination are useful in selection of patients for thrombolytic therapy.
PMCID: PMC3627161  PMID: 20663401
diffusion MRI, perfusion MRI, intra-arterial thrombolysis

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