The Effects of Raloxifene and Simvastatin on Plasma Lipids and Endothelium

Purpose: Raloxifene is a selective estrogen receptor modulator and an attractive alternative to estrogen replacement as it obviates the need for a progestin and does not increase C-reactive protein levels. We compared the effects of simvastatin and raloxifene treatments on the lipid profile, the levels of adhesion molecules and the endothelium dependent and independent vasoreactivity. Subjects & Methods: We treated 12 postmenopausal women with hypercholesterolemia and coronary artery disease with raloxifene 60 mg/day and simvastatin 20 mg/day in a randomized, double-blind, crossover study. Each treatment period was 8 weeks long with a 4-week washout interval. Plasma lipids and cellular adhesion molecules were evaluated and peripheral blood flow studies with venous occlusion plethysmography were performed. Results: Both simvastatin and raloxifene significantly reduced total [33% (27–40), 12% (0–24)] and LDL [44% (36–52), 16% (0–33)] cholesterol compared to baseline values (p < 0.05) but simvastatin was more effective than raloxifene (p < 0.005). None of the treatments had any significant effect on HDL cholesterol and triglyceride levels. Only raloxifene significantly reduced Lp(a) [18% (1–36)] and ICAM-1 [17% (8–25)] and VCAM-1 [24% (15–33)] plasma levels compared to baseline (p = 0.019, p < 0.0001 and p = 0.003, respectively). Hyperemic blood flow response on raloxifene was significantly higher compared to baseline [52% (0–105)], (p < 0.05), whereas no significant change was noted on simvastatin. Endothelium independent blood flow induced by nitroglycerine was not influenced by either active treatment. Conclusions: Raloxifene administration is associated with lower ICAM-1, VCAM-1 and Lp(a) plasma levels and enhanced endothelium dependent dilation compared to simvastatin although simvastatin is more powerful in total and LDL cholesterol reduction.     

Gender does not influence angiogenesis and arteriogenesis in a rabbit model of chronic hind limb ischemia

OBJECTIVE: Estrogen administration promotes angiogenesis and perfusion in oophorectomized rabbits with chronic limb ischemia. In the present study we tested whether gender affects angiogenesis and arteriogenesis in a rabbit model of chronic hind limb ischemia. METHODS AND RESULTS: Ischemia was induced in one hind limb of five oophorectomized (Ooph), seven non-oophorectomized (NonOoph) female and eight male New Zealand White rabbits by excision of the femoral artery. Ten days after the induction of ischemia (day 0) and at days 15 and 30 systolic calf blood pressure was measured in the ischemic and non-ischemic hind limbs. Revascularization in the ischemic limb was expressed as ischemic/normal limb blood pressure, capillary/muscle fiber density, and non-capillary, non-lymphatic vessels/muscle fiber density after examination of light microscopic sections taken from the abductor muscle of the ischemic limb at the time of death (day 30). Ischemic/normal blood pressure at day 30 in males was 0.62 +/- 0.22, in NonOoph 0.64 +/- 0.09 (P=ns vs. males) and in Ooph 0.39 +/- 0.05 (P<0.05 vs. males and NonOoph), (F=4.69, P=0.02). Ischemic capillary/muscle fiber in males was 0.96 +/- 0.09, in NonOoph 0.95 +/- 0.06 (P=ns vs. males) and in Ooph 0.83 +/- 0.09 (P<0.05 vs. males and NonOoph), (F=5.93, P=0.01). Ischemic non-capillary, non-lymphatic vessels/muscle fiber density in males was 0.11 +/- 0.02, in NonOoph 0.12 +/- 0.03 (P=ns vs. males) and in Ooph 0.08 +/- 0.02 (P<0.05 vs. NonOoph), (F=5.05, P=0.02). CONCLUSION: Gender does not influence angiogenesis and arteriogenesis in the rabbit model of chronic hind limb ischemia. However, estrogen deficiency induced by oophorectomy negatively affects angiogenesis and arteriogenesis.     

Massive suprachoroidal hemorrhage during cataract surgery: case report

A massive suprachoroidal hemorrhage is defined as a hemorrhage in the suprachoroidal space of sufficient volume either to cause extrusion of intraocular contents outside of the eye or to force the inner retinal surfaces into apposition ('kissing'). This is a very rare but one of the most serious complications of the intraocular surgeries. The authors describe a case of 84-year-old woman, who developed a massive suprachoroidal hemorrhage during cataract surgery. In our case, the main reason of expulsive hemorrhage development was a Valsalva effect, caused by unexpected cough during surgery. In a Valsalva maneuver, a sudden increase in venous pressure may lead to vessel-wall rupture, by an apparently excessive pressure gradient across the vessel wall. We present clinical and echographical study of this patient.     

A new approach towards pathogenesis and treatment of massive suprachoroidal hemorrhage

A massive suprachoroidal hemorrhage is a well-known, possibly serious complication of a variety of surgical procedures such as cataract extraction, penetrating keratoplasty, glaucoma-filtering operation, retinal detachment surgery and pars plana vitrectomy. It is defined as a hemorrhage, in the suprachoroidal space, of sufficient volume either to cause extrusion of intraocular contents outside of the eye or to force the inner retinal surfaces into apposition ("kissing"). Despite surgical interventions to drain the hemorrhage and establish normal anterior and posterior anatomic configurations to return of preoperative visual acuity is hard to prognosticate. This paper presents the current knowledge on the pathogenesis, risk factors, treatment of massive suprachoroidal hemorrhage.     

The risk factors for massive suprachoroidal hemorrhage in the material of the Department of Ophthalmology,Medical Academy in Bialystok from 1990 to 2000

PURPOSE: The aim of our study is evaluation of the risk factors for development of expulsive hemorrhage among patients operated in Department of Ophthalmology, Medical Academy in Bia?ystok from 1990 to 2000. MATERIAL AND METHODS: This was a retrospective study of 18 patients with massive suprachoroidal hemorrhage occurring in association with cataract and glaucoma surgery. RESULTS: The mean age of patients with expulsive hemorrhage was 69.5 years. There were 10 women (55.6%) and 8 men (44.4%). In the population of patients in whom the suprachoroidal hemorrhage occurred hypertension was present in 5 (27.7%) and diabetes in 3 (16.6%). 8 patients (44.4%) had reported atherosclerotic cardiovascular disease. 7 patients (38.8%) had a history of glaucoma, 6 (33.3%) had high myopia. 1 patient had posterior synechiae after uveitis. All surgeries, except one, were performed under local anesthesia. There were no associations between suprachoroidal hemorrhage development and season. CONCLUSION: The results of our study suggest, that the risk factors for the development of massive intraoperative suprachoroidal hemorrhage are: high myopia, glaucoma and systemic cardiovascular diseases. A knowledge of these risk factors can help the physician in identifying patients, who are at a greater risk of having massive suprachoroidal hemorrhage.     

Variations of Doppler blood flow parameters in central retinal artery in relation to position of sample volume

PURPOSE: To determine variability in measurements of Doppler blood flow parameters in central retinal artery in relation to sample volume location from the optic disc. MATERIAL AND METHOD: Eighty central retinal arteries were examined using color Doppler ultrasonography in 40 healthy volunteers (22 female, 18 male), aged 45 +/- 9 with 7.5 MHz linear-array probe. The measurements of blood velocities and resistance indices in the arteries were obtained at points where distance from optic disc surface ranged from 1.5 mm to 6 mm. RESULTS: Blood velocities increased significantly when sampled closer to the globe (r = -0.61, and r = -0.32 for peak-systolic and end-diastolic velocities, respectively). Mean peak-systolic velocities were 13.0 +/- 2.7 cm/s when distance 2.1 +/- 0.46 mm from optic disc, and 9.3 +/- 2.5 cm/s when distance 4.27 +/- 0.9 mm. Mean end-diastolic velocities were 4.3 +/- 1.2 cm/s and 3.6 +/- 1.1 cm/s, respectively. Resistance indices inclined to increase when the distance between the measurement site and the globe shortened. Resistance indices were 0.67 +/- 0.06 when measured closer to the globe and 0.60 +/- 0.06 when measured farther from it. CONCLUSION: Position of sample volume in relation to optic disc has to be taken into account and defined if measurements of blood flow Doppler parameters of the central retinal artery are to be reproducible.     

Clinical problems related to regeneration of cranial nerves supplying visual organ

This review paper discusses problems related to regeneration of cranial nerves III-VII after their traumatic injuries. Details pertinent to the regeneration of particular nerves are reviewed. The problem of peripheral aberrant regeneration is more vastly discussed, as it is believed to underly certain clinical syndromes of oculomotor misdirection.     

Optic nerve regeneration: contemporary views and perspectives of clinical use

Recent extensive advances in neuroscience not only proved that optic nerve has a capacity for functional repair, but made its regeneration a reality in laboratory mammals. Today it is evident that optic nerve after axonotmesis displays signs of very active regeneration. Nevertheless, the regeneration is inhibited by a number of factors acting in the environment of normal CNS. Inhibitors secreted by oligodendrocytes and deposited in the layer of myelin attenuate migration of macrophages and process of phagocytosis, which is indispensable for axon regeneration. Astrocytes, which secrete substances supporting nerve regeneration, can not migrate to the injured axons. Glial scar formation prevent axon regrowth and revascularisation. Moreover, immediate expression of certain genes causes axotomised retinal ganglion cells to undergo process of programmed cell death--apoptosis. At present, regeneration of the optic nerve may be successfully promoted in laboratory set-up with substances which can slow down ganglion cells apoptosis and promote axon regrowth. Peripheral nerve bridges and embryonic transplants offer the regenerating axons more friendly environment than that of the normal, matured CNS. One problem, which can not yet be successfully addressed, is how to lead regrowing axons back appropriately to their original targets to reform patterned connections.     

Monoclonal antibody detection of a circulating tumor-associated antigen. I. Presence of antigen in sera of patients with colorectal,gastric, and pancreatic carcinoma

Hybridoma-secreted monoclonal anti-colorectal carcinoma antibodies 19-9, 52a, and C₄ 14 bind specifically to cells of colorectal, gastric, and pancreatic carcinoma in tissue culture. The assay for the detection of antigen in human sera is based on the inhibition of binding of monoclonal antibodies to target preparations of colorectal carcinoma cells. Binding of monoclonal antibody 52a was inhibited more than 12% by 163 of 255 sera from patients from various stages of carcinoma of colon and rectum, by 45 of 49 sera from patients with pancreatic carcinoma, and by 8 of 11 sera from patients with gastric carcinoma. By contrast, only 7 of 89 sera from patients with other malignancies and 2 of 108 sera from healthy donors inhibited binding of this monoclonal antibody by more than 12%. These studies show the potential usefulness of monoclonal antibodies in the diagnosis of human malignancy.