Age-Related Maculopathy: a biochemical and immunohistochemical study

Age-related maculopathy (ARM) is an age-related degenerative disorder of the central part of the retina, the macula lutea (yellow spot). Essentially, ARM is a clinical diagnosis based on funduscopical changes. It is customary nowadays to call the late stages of ARM, geographic atrophy and neovascular (disciform) macular degeneration, age-related macular degeneration (AMD)(Bird, et ai., 1995). These late stages result in severe and irreversible visual impairment and tend to progress to the center of the macula (the fovea), where visual acuity is affected most. Because AMD is usually a bilateral disorder, affected people loose their ability to read, drive, and watch television (Macular-photocoagulation-study-group, 1993). The prevalence of AMD is 1-7% in people over 60, up to 14% over age 85. Obviously, the number of people affected by AMD will enlarge, because of the increasing age of the population (Ferris, 1983; Klein, el ai., 1992; Leibowitz, el ai., 1980; Vinding, 1989; Vingerling, et ai., 1995c). In fact, AMD is the mosl common cause of blindness in the elderly in the weslern world and it is estimated that 640.000 people in the USA aged 75 years or older have signs of AMD (Klein, et ai., 1992), while in The Netherlands 57.000 persons suffer from AMD in at least one eye (Vingerling, et ai., 1995d). Although this disease has been known for more than a century (Haab, 1888), knowledge on the patllOgenesis of the affliction is still incomplete. Some risk-factors for ARM have been found in epidemiologic studies. Current smokers have a three times increased risk to develop this disease (Vingerling, et ai., 1995b), and cardiovascular diseases and early-menopause are reported to be risk-factors as well (Vingerling, et ai., 1995a; Vingerling, et aI., 1995e). There is still no adequate therapy for the majority of people disabled by AMD. Therefore, it is necessary to intensify the research on ARM and AMD in order to understand the pathogenesis of this disease. This knowledge may eventually lead to an adequate therapy or to preventive measures for this severely invalidating disease

Soft tissue sarcomas at a glance: clinical, histological, and MR imaging features of malignant extremity soft tissue tumors

Soft tissue sarcomas comprise approximately 1% of malignant tumors. There are more than 50 subtypes, but pleomorphic sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor account for 75%. Differentiation between these subtypes is difficult because they often present with a painless enlarging mass, and share many histological and MR imaging features. Nonetheless, subdifferentiation is important because the different subtypes have different prognoses and therapeutic strategies. In this manuscript we discuss the clinical, histological, and MR imaging features of soft tissue sarcomas according to the WHO classification. An overview is provided and differentiating features are discussed that can help to narrow down the differential diagnosis

Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM

Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM

Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation

BACKGROUND: Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation. METHODS AND RESULTS: End-diastolic septal wall thickness was significantly increased in patients with HCM (25.8+/-2.9 mm) in comparison with cardiac transplant recipients (control subjects: 11.4+/-3.0 mm; P<0.05). Although the diameter of the left anterior descending coronary artery was similar in both groups (3.0+/-0.8 versus 3.0+/-0.5 mm, P=NS), the coronary resistance reserve (CRR=CRRbasal/CRRhyperemic), corrected for extravascular compression (end-diastolic left ventricular pressure), was reduced to 1.5+/-0.6 in HCM (P<.05; control, 2.6+/-0.8). Arteriolar lumen (AL) divided by wall area was lower in HCM (21+/-5% versus 30+/-4%; P<.05), and capillary density tended to decrease (from 1824+/-424 to 1445+/-513 per mm2, P=.11) in HCM. CRR was linearly related to normalized AL according to the formula CRR=O.1 AL-0.45 (r=.57; P<.05). Further analysis revealed that CRR, AL, and capillary density were all linearly related to the degree of hypertrophy. CONCLUSIONS: Decrements in CRR were related to changes of the coronary microcirculation. Both the decrease in CRR and these changes in the coronary microcirculation were related to the degree of hypertrophy. All these factors might contribute to the well-known occurrence of ischemia in this patient group