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Biomedical subjects

P L Lip

Publications and source records attributed to P L Lip.

At least 19 recordsLinked to original sources

The angiopoietin/Tie-2 system in proliferative sickle retinopathy: relation to vascular endothelial growth factor, its soluble receptor Flt-1 and von Willebrand factor, and to the effects of laser treatment.

AIM: To determine plasma levels of angiopoietin-1 and angiopoietin-2 (Ang-1, Ang-2), their soluble receptor Tie-2, vascular endothelial growth factor (VEGF), its soluble receptor Flt-1 (as indices of angiogenesis), and von Willebrand factor (vWf, marking endothelial damage/dysfunction) in sickle cell disease (SCD) patients with proliferative sickle retinopathy (PSR), with non-proliferative retinopathy (NPR), or no retinopathy (NR) and in control subjects with normal haemoglobin (AA subjects). In addition, to determine changes with panretinal laser photocoagulation (PRP) therapy. METHODS: Research indices were measured (ELISA) in 24 SCD patients who had PSR, 16 with NPR, 16 with NR, and from 23 AA subjects. Eight patients received PRP therapy and plasma was obtained before laser treatment and at 6 months after the last PRP session. RESULTS: Ang-1, Ang-2, VEGF, and vWf (but not Tie-2 or sFlt-1) were raised in SCD patients compared to AA subjects (p<0.01) but there were no differences among the three SCD subgroups. Significant correlations were between Ang-1 and VEGF, Ang-1 and Tie-2, and VEGF and sFlt-1 in patients with SCD (r = 0.67-0.88). Plasma Ang-2, VEGF, sFlt-1, and vWf levels did not change, but Ang-1 fell and Tie-2 rose significantly following PRP therapy. CONCLUSIONS: SCD patients have raised plasma angiopoietins (Ang-1, Ang-2), VEGF, and vWf compared to AA subjects. These indices did not differ according to severity of retinopathy and only limited changes occurred following PRP. The elevated growth factor levels in SCD may have obscured any association with retinopathy.

Adult↗

Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: effects of laser photocoagulation and angiotensin receptor blockade.

BACKGROUND: Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors. METHODS: Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA. RESULTS: VEGF (p<0.001) and Ang-2 levels (p<0.001) were significantly higher in 93 diabetic patients compared to 20 healthy controls, with the highest levels in grade 2 and grade 3 diabetic retinopathy (p<0.05). Tie-2 was lower in diabetics compared to controls (p = 0.008), with no significant differences between the diabetic subgroups. Overall, VEGF significantly correlated with Ang-2 (p<0.001) and tie-2 (p = 0.004) but the correlation between Ang-2 and tie-2 levels was not significant (p = 0.065). Among diabetic patients only, VEGF levels were significantly correlated with Ang-2 (p<0.001) and tie-2 (p<0.001); the correlation between Ang-2 and tie-2 levels was also significant (p<0.001). There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy. CONCLUSION: Increased plasma levels of VEGF and Ang-2, as well as lower soluble tie-2, were found in diabetic patients. The highest VEGF and Ang-2 levels were seen among patients with pre-proliferative and proliferative retinopathy, but there was no relation of tie-2 to the severity of retinopathy. As the majority of previous research into Ang-2 and tie-2 has been in relation to angiogenesis and malignancy, the present study would suggest that Ang-2 and tie-2 may be used as potential indices of angiogenesis in diabetes mellitus (in addition to VEGF) and may help elucidate the role of the angiopoietin/tie-2 system in this condition.

Acrylates↗

Hypertension and the eye: changing perspectives.

Systemic hypertension is a common condition associated with significant morbidity and mortality. Hypertension confers cardiovascular risk by causing target-organ damage that includes retinopathy in addition to heart disease, stroke, renal insufficiency and peripheral vascular disease. The recognition of hypertensive retinopathy is important in cardiovascular risk stratification of hypertensive individuals. This review reevaluates the changing perspectives in the pathophysiology, classification and prognostic significance of fundal lesions in hypertensives.

Eye Diseases↗

Plasma vascular endothelial growth factor, soluble VEGF receptor FLT-1, and von Willebrand factor in glaucoma.

AIM: To investigate plasma indices of vascular permeability (vascular endothelial growth factor, VEGF-also an index of angiogenesis, as well as the soluble receptor for VEGF, sFlt-1) and endothelial damage/dysfunction (von Willebrand factor, vWf) in glaucoma. METHODS: Citrated plasma was assayed for VEGF, sFlt-1, and vWf (all ELISA) in a cross sectional study of 50 patients (20 male; mean age 63.9 years, SD 10.5) with glaucoma: 26 had normal tension glaucoma (NTG) and 24 had primary open angle glaucoma (POAG), who were compared with 26 healthy controls (mean age 73.4 years, SD 9.2). RESULTS: Median (interquartile range, IQR) levels of VEGF were significantly elevated in patients with NTG and POAG compared to healthy controls (Kruskal-Wallis test, p<0.001). Similarly, mean (SD) vWF levels were abnormal in NTG and POAG compared to healthy controls (one way ANOVA, p<0.001). Median levels of sFlt-1 were significantly lower in patients with NTG and POAG, when compared to healthy controls (Kruskal-Wallis test, p<0.001; p<0.05 with Tukey's post hoc test for controls v POAG). There were no significant differences in VEGF, sFlt-1 or vWf levels between the NTG and POAG groups (Tukey's test, all p=NS). In both NTG and POAG groups, there was a significant correlation between VEGF and sFlt-1 (Spearman, NTG: r=0.6517, p=0.001; POAG: r=0.6017, p=0.008). There were no significant correlations between VEGF and sFlt-1, or with vWf among the controls. CONCLUSIONS: The pathogenesis of optic nerve damage in both NTG and POAG may be associated with abnormal vascular permeability and endothelial damage/dysfunction, as indicated by abnormal plasma VEGF and vWf levels in these patients.

Aged↗

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction.

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Aged↗

Idiopathic polypoidal choroidal vasculopathy: a disease with diverse clinical spectrum and systemic associations.

PURPOSE: To report the clinical findings, angiographic results, clinical course, response to laser photocoagulation and systemic-associations in a group of patients with idiopathic polypoidal choroidal vasculopathy (IPCV). METHODS: All patients with IPCV attending the macular clinic underwent a complete ocular examination, and fluorescein and indocyanine green angiography. In addition, a systemic examination including blood pressure, full blood count, plasma viscosity and coagulation status of patients was carried out. RESULTS: We present a series of 5 patients (7 eyes) with clinical and angiographic evidence of IPCV with follow-up of 3-6 years. We report diverse demographic and clinical manifestations. One patient had polypoidal lesions found at the peripheral retina (anterior to equator) of both eyes. Three patients were treated with laser photocoagulation and achieved stable vision; 2 patients who had no laser treatment experienced deteriorated vision, one of whom had a vitrectomy. One patient was hypertensive, 2 patients were found to have raised plasma viscosity, and 1 patient had thrombocytopenia. CONCLUSIONS: The clinical spectrum of IPCV is wider than previously documented. It is a distinct clinical entity which should be differentiated from other forms of haemorrhagic and exudative maculopathy. The availability of indocyanine green angiography has allowed increased recognition of these cases. Early selective laser treatment on lesions affecting maculae-could stabilise the disease. Its association with systemic cardiovascular disease and blood disorder may predispose to the recurrence of haemorrhagic events in this entity.

Adolescent↗

Plasma VEGF and soluble VEGF receptor FLT-1 in proliferative retinopathy: relationship to endothelial dysfunction and laser treatment.

PURPOSE: To study plasma levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), its soluble receptor (sFlt-1) and von Willebrand factor (vWf, an index of endothelial damage or dysfunction) in patients with proliferative retinopathy and corresponding changes in plasma levels after pan-retinal photocoagulation (PRP). METHODS: Eighteen patients (10 men; age, 57+/-16 years, mean +/- SD) with proliferative retinopathy secondary to diabetes (n = 13) and ischemic retinal vein occlusion (n = 5) with no previous PRP therapy were studied. Blood samples were obtained before and at 4 months after the last PRP session. Baseline (prelaser) plasma levels of VEGF, sFlt-1, and vWf (all by ELISA) were compared with levels in 16 diabetic patients with background retinopathy ("hospital controls"), and 18 healthy, age- and sex-matched "healthy controls." RESULTS: Patients with proliferative retinopathy had significantly raised plasma VEGF when compared with both control groups (P = 0.001). Patients with proliferative retinopathy and hospital controls had significantly raised plasma vWf levels when compared with healthy controls (P = 0.012). There was no difference in sFlt-1 levels between patients and controls (P = 0.162). After PRP, there was a significant reduction in plasma VEGF levels at 4 months' follow-up (P < 0.001), but no significant changes in plasma sFlt-1 or vWf levels. Patients with complete resolution of neovascularization had a trend toward lower median VEGF levels (80 versus 150 pg/ml, P = 0.062), but vWf levels (P = 0.50) and sFlt-1 (P = 0.479) were not statistically different. Baseline VEGF and sFlt-1 levels were significantly correlated (Spearman r = 0.505, P = 0.032) but after PRP at 4 months' follow-up, this was no longer significant (r = -0.269, P = 0.28). CONCLUSIONS: In this pilot study, patients with proliferative retinopathy demonstrate elevated peripheral markers of angiogenesis and endothelial dysfunction, suggesting a role for these processes in the pathogenesis of this condition. A fall in levels of VEGF after successful laser treatment may provide an opportunity for monitoring disease progression or relapse via a blood sample.

Diabetes Complications↗

Sorsby's fundus dystrophy: a case report of 24 years follow-up with electrodiagnostic tests and indocyanine green angiography.

PURPOSE: Five families with dominantly inherited macular dystrophy were originally described by Sorsby et al. in 1949. Key features include early bilateral central visual loss secondary to either choroidal neovascularisation or central geographical atrophy and late progressive chorioretinal atrophy. We report a member of one of the original families who has been studied with a series of investigations over a long time, providing important information on differences in the phenotype and natural history of a rare genetically determined macular dystrophy. METHODS: The patient has been followed up for the last 24 years, from asymptomatic to full manifestation of Sorsby's fundus dystrophy. Series of fundus photographs, colour vision, dark adaptation and electrodiagnostic tests were performed. The disease was also studied with fundus fluorescein angiography and indocyanine green angiography. RESULTS: Unlike her other family members, who were reported in other studies as all having rapid loss of vision secondary to disciform macular disease, our patient has a unique clinical course in that she has a progressive bilateral central and generalised chorioretinal atrophy with a well-preserved minute central island of fovea. Nyctalopia was her early and only symptom. There was evidence of central scotoma, tritanopia and mild abnormality in dark adaptation. Rod function was affected earlier and to a larger degree than cone function. CONCLUSIONS: The overall features suggest phenotypic variability within a family in this autosomal dominant macular dystrophy. The findings from indocyanine green angiography and a consecutive series of electrodiagnostic tests in this condition support the theory of partial choroidal hypoperfusion and an interesting progressive rod-cone dystrophy as part of the pathophysiology.

Adult↗

Do intraocular angiotensin II levels, plasma prothrombotic factors and endothelial dysfunction contribute to proliferative diabetic retinopathy?

PURPOSE: To investigate whether diabetic retinopathy (DR) is associated with abnormalities in: (i) aqueous humour Angiotensin I (Ang I) and Angiotensin II (Ang II) levels; and (ii) plasma Ang I, soluble P-selectin, lipoprotein (a) (Lp(a)), endothelial markers and haemorheological abnormalities. METHODS: Cross-sectional study of diabetic patients and healthy controls undergoing cataract surgery. RESULTS: 21 diabetic patients (12 males; mean age 67.0 years) were studied. Plasma levels of Ang II were lower in diabetics compared with controls (p<0.05). There were no differences in mean aqueous Ang I and Ang II levels in diabetics with or without proliferative DR compared with controls. Mean systolic blood pressure was higher in Group 1 patients (p=0.02). Patients with DR also demonstrated high Lp (a) and abnormal haemorheological factors (fibrinogen, white cell count). CONCLUSION: Ang I and Ang II do not significantly contribute to the pathogenesis of DR. Patients with DR also had abnormal Lp (a) and haemorheological factors. The role of hypertension in the pathogenesis of DR needs further evaluation.

Aged↗

Abnormalities in haemorheological factors and lipoprotein (a) in retinal vascular occlusion: implications for increased vascular risk.

BACKGROUND: The pathogenesis of retinal vascular occlusion (RVO), which includes patients with retinal vein or artery occlusions, may be associated with abnormalities of rheology and coagulation. These abnormalities have previously been linked with an increased risk of cardiovascular disease and stroke. AIM, PATIENTS AND METHODS: To investigate changes in haemorheological factors (plasma viscosity, haematocrit, haemoglobin, white cell count (WCC), plasma fibrinogen (CLAUSS), soluble adhesion molecule P-selectin (associated with platelet activity and atherosclerosis; ELISA), von Willebrand factor (vWf, an index of endothelial dysfunction; ELISA), fibrin D-dimer (ELISA), lipoprotein(a) (Lp(a), immunoturbidometric assay) and serum lipids, we conducted a cross-sectional case-controlled study of 49 patients (37 men; mean age 66.9 years, SD 12.1 years) with RVO; 34 patients had retinal vein occlusion, whilst 15 had retinal artery occlusion. Their results were compared with those in 36 healthy controls (21 men; mean age 63.7 years, SD 14.8 years). RESULTS: Patients with retinal vein occlusion and retinal artery occlusion had higher systolic and diastolic blood pressures compared with controls (both p < 0.0001). These patients also had significantly elevated levels of plasma viscosity, haematocrit, haemoglobin, plasma fibrinogen, PAI, fibrin D-dimer and serum Lp(a) compared with controls. Apart from a reduction in blood pressure, there were no significant differences in the indices measured in patients with retinal vein occlusion when levels measured during their first and second visits were compared. In patients with retinal artery occlusion mean plasma PAI levels were significantly lower at visit 2 compared with visit 1. Plasma viscosity was significantly correlated with fibrinogen (r = 0.63, p < 0.001), systolic blood pressure (r = 0.33, p = 0.03) and cholesterol (r = 0.32, p = 0.04), while P-selectin was correlated with Lp(a) levels (r = 0.38, p = 0.03). CONCLUSION: This study suggests that abnormalities in haemorheological factors, fibrinogen and Lp(a) are present in patients with retinal vein occlusion and retinal artery occlusion. These abnormalities appear to persist even at follow-up examination 4-6 weeks later. Abnormalities in haemorheological factors, fibrinogen and Lp(a) may have a role in the pathogenesis of retinal vein occlusion and retinal artery occlusion, perhaps acting synergistically with clinical risk factors such as blood pressure. In addition, as haemorheological factors, fibrinogen and Lp(a) are associated with vascular disease, these findings in patients with RVO may potentially contribute to an increased risk of cardiovascular disease and stroke.

Aged↗

Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy.

Although the arterial tree is exposed to increased pressure in hypertensive patients, paradoxically, the complications of hypertension (heart attacks, stroke) are mainly thrombotic rather than hemorrhagic. Patients with left ventricular (LV) hypertrophy are at high risk of the complications of hypertension. We performed a cross-sectional study of 178 patients attending a hypertension clinic in a city center teaching hospital, and measured plasma levels of the soluble adhesion molecule P-selectin (associated with platelet activity/function and atherosclerosis), the von Willebrand factor (vWf; a marker of endothelial dysfunction), fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor (PAI, an index of fibrinolysis), lipoprotein(a) (Lp(a), associated with thrombogenesis and atherogenesis) and hemorheological indexes (fibrinogen, hematocrit, plasma viscosity, hemoglobin) in patients with essential hypertension, in whom the LV mass and LV mass index were determined using echocardiography. The 178 patients (86 men, mean age 54 +/- 15 years) were compared with 47 normotensive healthy controls (aged 56 +/- 20 years). Hypertensive patients had higher P-selectin, PAI, vWf, fibrin D-dimer, Lp(a), plasma fibrinogen, and plasma viscosity when compared with controls. Black hypertensive patients had higher Lp(a) levels and LV septal and posterior wall thickness on echocardiography, but lower plasma PAI levels. Patients with LV hypertrophy (defined as a LV mass index > 134 g/m2 in men or > 110 g/m2 in women) had higher plasma fibrinogen compared with those without LV hypertrophy. Systolic blood pressures were significantly correlated to age, plasma viscosity, plasma fibrinogen, and vWf. Diastolic blood pressures were significantly correlated with age and plasma fibrinogen. Fibrinogen levels were correlated with LV mass, LV mass index, left atrial size, plasma viscosity, and vWf. Fibrin D-dimer levels were significantly correlated with vWf and fibrinogen levels. Thus, hypertensive patients have high plasma fibrinogen levels, thrombogenesis, and impaired fibrinolysis (as indicated by high D-dimer and PAI levels, respectively), platelet activation (raised soluble P-selectin), and endothelial dysfunction (high vWF). The high plasma fibrinogen levels were related to blood pressures, LV mass index (and LV hypertrophy), and left atrial size. These abnormalities in hemorheologic factors and markers of thrombogenesis and endothelial function may act synergistically to increase the risk of thrombogenesis and atherosclerosis in hypertensive patients.

Adult↗