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Biomedical subjects

Harry Leung

Publications and source records attributed to Harry Leung.

12 recordsLinked to original sources

Intraconal superior ophthalmic vein embolisation for carotid cavernous fistula.

A 53-year-old man presented with a longstanding carotid cavernous fistula that could not be embolised completely via the femoral route. A superior ophthalmic vein approach was necessary; however, the vein was thrombosed anteriorly and only intraconal cannulation was possible. The vein was accessed via a superior lid crease approach and the fistula successfully embolised. Whilst utilising the superior ophthalmic vein is well described in the literature, to our knowledge, needing to access the intraconal portion of the vein has not previously been reported.

Carotid-Cavernous Sinus Fistula↗

Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells.

Normal bone marrow (BM) contains T cells whose function and origin are poorly understood. We observed that CD8+ T cells in BM consist chiefly of CCR7+ L-selectin+ central memory cells (TCMs). Adoptively transferred TCMs accumulated more efficiently in the BM than naive and effector T cells. Intravital microscopy (IVM) showed that TCMs roll efficiently in BM microvessels via L-, P-, and E-selectin, whereas firm arrest required the VCAM-1/alpha4beta1 pathway. alpha4beta1 integrin activation did not depend on pertussis toxin (PTX)-sensitive Galphai proteins but was reduced by anti-CXCL12. In contrast, TCM diapedesis did not require CXCL12 but was blocked by PTX. After extravasation, TCMs displayed agile movement within BM cavities, remained viable, and mounted potent antigen-specific recall responses for at least two months. Thus, the BM functions as a major reservoir for TCMs by providing specific recruitment signals that act in sequence to mediate the constitutive recruitment of TCMs from the blood.

Adoptive Transfer↗

Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes.

Mature recirculating B cells are generally assumed to exist in follicular niches in secondary lymphoid organs, and these cells mediate T-dependent humoral immune responses. We show here that a large proportion of mature B lymphocytes occupy an anatomically and functionally distinct perisinusoidal niche in the bone marrow. Perisinusoidal B cells circulate freely, as revealed by parabiosis studies. However, unlike their counterparts in the follicular niche, these cells are capable of being activated in situ by blood-borne microbes in a T-independent manner to generate specific IgM antibodies. The bone marrow represents a unique type of secondary lymphoid organ in which mature B cells are strategically positioned in the path of circulating microbes.

Animals↗

Retinal vessel diameter and open-angle glaucoma: the Blue Mountains Eye Study.

PURPOSE: To examine the relationship between open-angle glaucoma (OAG) and retinal vessel diameter among baseline participants in the Blue Mountains Eye Study. DESIGN: Population-based cross-sectional study. PARTICIPANTS: The study included 3654 persons older than 49 years, representing 82.4% of permanent residents living in an area west of Sydney. METHODS: Participants had a detailed eye examination, including automated perimetry and stereo optic disc photography. A computer-assisted program measured retinal vessel diameters from digitized photographs of right eyes. MAIN OUTCOME MEASURES: Open-angle glaucoma was diagnosed from matching visual field defects and optic disc cupping, without reference to intraocular pressure (IOP) level. Ocular hypertension was defined as IOP of >21 mmHg in either eye, without matching glaucomatous optic disc and field changes. Average retinal vessel diameters, measured from right eyes, were summarized as arteriolar and venular equivalents. The lowest quintile of the arteriolar equivalent or arteriole-to-venule ratio was used to define generalized retinal arteriolar narrowing. RESULTS: The study included 3314 participants, after excluding those with incomplete data or nonglaucomatous optic nerve disease. Of persons included, 59 (1.8%) had evidence of glaucomatous damage affecting the right eye, 3065 (92.5%) had no damage to either eye, and 163 (4.9%) had ocular hypertension. Right eyes with glaucomatous damage had significantly narrower retinal arteriolar diameters (183+/-2.6 microm) than eyes without glaucoma (194+/-0.4 microm, P = 0.0001) or eyes with ocular hypertension (195+/-1.6 microm, P = 0.0002), after adjusting for age, mean arterial blood pressure, and other confounding variables, including refraction. Right eyes with glaucomatous damage were at least 2 times more likely to have generalized retinal arteriolar narrowing than eyes without glaucoma (odds ratio, 2.7; 95% confidence interval, 1.5-4.8). CONCLUSIONS: These population-based data suggest that generalized retinal arteriolar narrowing, an indicator of localized vascular change, is significantly associated with optic nerve damage caused by OAG. It is not clear whether such a retinal arteriolar change reflects an ischemic process leading to optic nerve damage or results from loss of retinal neurons secondary to glaucoma.

Aged↗

Does hormone replacement therapy influence retinal microvascular caliber?

Previous population-based data suggest that retinal arteriolar diameter is wider in women than in men. Estrogen exposures could account for this difference. To evaluate the effects of HRT on small blood vessels, we assessed the relationship between use of hormone replacement therapy (HRT) and retinal microvascular diameter in older women in the Blue Mountains Eye Study baseline population (n = 1993, age >/= 49 years). Information on HRT use was recorded by trained interviewers. A computer-assisted program measured retinal vessel diameters from digitized photographs. Average arteriolar diameter was calculated as the central retinal arteriolar equivalent (CRAE); the lowest quintile of CRAE was considered generalized arteriolar narrowing. Of the 1897 women with complete data, 79 (4%) were premenopausal and 315 (17%), 224 (12%), and 1279 (67%) were current, past, and never HRT users, respectively. Among women aged < 65 years, multivariate-adjusted mean CRAE for the four groups was 196, 198, 201, and 200 microm (P < 0.0001), respectively. Among postmenopausal women >/= 65 years, multivariate-adjusted mean CRAE was 187, 188, 191 microm (P < 0.0001), respectively, for current, past, and never users. Current HRT users were 40% more likely than never users to have generalized arteriolar narrowing (95% confidence interval 1.0-2.1). It appears that the use of HRT in older women may not have any long-term vasodilatory effects on retinal arterioles. These data do not support our hypothesis that exogenous estrogen exposures account for observed wider retinal arteriolar diameters in women.

Aged↗

Impact of current and past blood pressure on retinal arteriolar diameter in an older population.

OBJECTIVE: To examine the effects of current and past blood pressure on retinal arteriolar diameter in a general older population. DESIGN: Cross-sectional and longitudinal studies. SETTING: Population-based cohort study of older residents from an area west of Sydney, Australia. PARTICIPANTS: Two thousand three hundred and thirty-five individuals (n = 2335) (aged > or = 54 years) who attended the 5-year follow-up Blue Mountains Eye Study during 1997-99. MAIN OUTCOME MEASURES: A computer-assisted method measured vessel diameters from digitized right eye retinal photographs. The narrowest quintile of central retinal arteriolar equivalent or arteriole-to-venule ratio (AVR) defined generalized arteriolar narrowing. Blood pressure was measured using a mercury sphygmomanometer. RESULTS: After simultaneous adjustment for age, sex, body mass index, smoking and current or past blood pressure, elevated levels of both current and past blood pressure were associated with narrower retinal arterioles [Ptrend = 0.009 and 0.007 for current and past systolic blood pressure (SBP), respectively] and lower AVR [Ptrend = 0.001 and 0.0009 for current and past diastolic blood pressure (DBP), respectively]. Generalized arteriolar narrowing was associated with both current blood pressure [adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.8 for the highest versus lowest quintile of current DBP] and past blood pressure (adjusted OR 1.7, 95% CI 1.1-2.6, for the highest versus lowest quintile of past DBP). Hypertension duration or control status at baseline had no additional effect on arteriolar diameter after adjusting for current blood pressure. CONCLUSIONS: Our data document the independent effects of both current and past blood pressure on small vessel calibre in the retina, suggesting that retinal arteriolar narrowing may result from the cumulative effects of long-standing hypertension.

Aged↗

Lacunar thalamic stroke proclivity for falls.

Small ischaemic lesions strategically placed could give rise to specific clinical manifestations depending on the location and size of the lesion. We present the case of five patients with imbalance and falls with no other neurological findings. The computed tomographic scan showed a lacunar infarct in the right or left thalamus. The tendency to fall may complicate rehabilitation. The possible physiological mechanisms are discussed.

Accidental Falls↗

Hypertensive retinal vessel wall signs in a general older population: the Blue Mountains Eye Study.

To describe cross-sectional relations between hypertension and retinal vessel wall signs in an older white population. These signs were defined from fundus photographs in 3654 Blue Mountains Eye Study participants > or =49 years of age. Focal arteriolar narrowing and arteriovenous nicking were graded through the use of standard protocol. Photographs were digitized to measure retinal vessel diameters. Average arteriolar diameter, summarized as central retinal arteriolar equivalent and arteriole-to-venule ratio, were used as indexes of generalized arteriolar narrowing. Blood pressure was measured with the use of a mercury sphygmomanometer. Hypertension was defined through the use of antihypertensive medications, systolic blood pressure > or =160 mm Hg, or diastolic blood pressure > or =95 mm Hg. Hypertension was categorized as controlled (using medication, normal blood pressure), uncontrolled (using medication, high blood pressure), or untreated (not using medication). Hypertensive subjects had higher prevalence of all retinal microvascular signs. After adjusting for age, gender, body mass index, and smoking, persons with controlled (18.2%), uncontrolled (13.8%), or untreated hypertension (13.8%) were significantly more likely than normotensive subjects (54.2%) to have (a) lower central retinal arteriolar equivalent: adjusted odds ratios 1.5, (95% CI, 1.1 to 1.9), 2.1 (1.6 to 2.7), and 2.1 (1.6 to 2.7), respectively, and lower arteriole-to-venule ratio: 1.3 (1.0 to 1.6), 1.4 (1.1 to 1.8), and 1.7 (1.3 to 2.2), respectively; (b) focal arteriolar narrowing: 1.3 (0.9 to 1.9), 2.2 (1.5 to 3.2), and 2.5 (1.8 to 3.6), respectively; and (c) arteriovenous nicking: 1.3 (0.9 to 1.8), 2.3 (1.6 to 3.2), and 1.9 (1.3 to 2.7), respectively. Our findings demonstrate a strong relation between presence and severity of hypertension and retinal microvascular structural changes.

Aged↗

Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis.

Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor-based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of beta 1 integrins and MT1-matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered beta 1 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis.

Actins↗

Computer-assisted retinal vessel measurement in an older population: correlation between right and left eyes.

This study assessed the correlation between computer-assisted retinal vessel measurements of right and left eyes, from subjects in a defined, community-based older population. Retinal photographs from participants in the Blue Mountains Eye Study were digitized. All retinal arterioles and venules located 0.5-1.0 disc diameters from the optic disc margin were identified and a computer program measured their diameters. Pearson correlation (R2) statistic was used to assess the correlation in a random subsample of 1546 images. Substantial correlation between right and left eye measurements was found for summary indices of retinal arterioles (R2 = 0.70) and venules (R2 = 0.77). Higher correlation was found for intragrader (R2 0.75-079) than for intergrader assessment (R2 0.67-0.72). Moderate correlation was found in arteriole-to-venule ratio assessed by the same (R2 = 0.57) or different (R2 = 0.52) graders. Measurements from one eye can thus adequately represent the retinal vessel diameters of a person.

Aged↗

Relationships between age, blood pressure, and retinal vessel diameters in an older population.

PURPOSE: To describe the cross-sectional relationships between age, blood pressure (BP), and quantitative measures of retinal vessel diameters in an older Australian population. METHODS: Retinal photographs from right eyes of participants (n = 3654, aged 49+ years) in the Blue Mountains Eye study taken during baseline examinations (1992-1994) were digitized. The width of all retinal vessels located 0.5 to 1.0 disc diameters from the disc margin was measured by a computer-assisted method. Summarized estimates for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) represent average retinal vessel diameters. The arteriole-to-venule ratio (AVR) was calculated. Associations between age and BP and CRAE, CRVE, and AVR were assessed with generalized linear models. RESULTS: Retinal vessel diameters decreased with increasing age in both men and women. CRAE and CRVE decreased by 4.8 microm and 4.1 microm, respectively, per decade increase in age, after adjusting for sex and mean arterial blood pressure. Mean AVR declined by 0.01 for each increasing decade of age, until 79 years. After adjustment for age, sex, smoking, and body mass index, CRAE, CRVE and AVR were all significantly and inversely associated with BP. For every 10-mm Hg increase in mean arterial blood pressure, AVR decreased by 0.012 and CRAE and CRVE decreased by 3.5 microm and 0.96 microm, respectively. CONCLUSIONS: Retinal arteriolar and venular diameters narrow with increasing age, and these parameters are inversely related to BP, independent of age, gender, and smoking. The findings are consistent with those from the Atherosclerosis Risk in Communities Study suggesting that decreased retinal vessel diameters may reflect microvascular damage from elevated blood pressure.

Aged↗

Confused and disturbed behavior in the elderly following silent frontal lobe infarction.

It is unclear whether silent frontal lobe infarction is truly asymptomatic; frontal behavioral syndromes following strokes have rarely been reported. We studied 12 elderly patients with silent frontal lobe infarction who were exhibiting confused and disturbed behavior. Ten were male and two female; their ages ranged from 68 to 79 (mean 78). Three groups of symptom clusters emerged: changes in mood and emotional behavior, cognitive deterioration with minor psychiatric symptoms, and a confusional state. When related to the CT scan location, three regions were identified: predominantly orbitofrontal, deep white matter and caudate, and border-zones, respectively. These findings were related to what is known about the neuroanatomic location of the lesions and the role of the frontal subcortical circuitry in relation to behavior. The different manifestations could be explained by damage to the frontal lobe or interruption of the complex frontal subcortical circuits.

Aged↗