bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion Formulas between Automated-Perimetry Indexes as Measured by Two Different Types of Instrument
Authors: Papp András , Kis Krisztina , Németh János
Published: April 2003

Purpose: Comparison between the results of measurements made using different types of automated-perimetry equipment is difficult, because of the lack of standardisation. The purpose of the study was to compare the two main indexes, mean deviation or mean defect (MD) and pattern standard deviation (PSD), as measured by two widely used instruments (Interzeag Octopus 500EZ and Humphrey Field Analyser 740) in the same group of patients. Patients and Methods: Thirty eyes of 17 patients with different stages of primary open-angle glaucoma were tested, and for 25 eyes the indexes measured using program G1 of the Octopus perimetry instrument were compared with those from program C30-2 of the Humphrey Field Analyser. Results: Using the one-tailed Student t test, a significant difference was found between the MD and the PSD values of the Humphrey and of the Octopus perimetry equipments. However, subsequent use of the conversion formulas to adjust the measurements then indicated a good correlation between the two instruments (MD: r = 0.91; PSD: r = 0.79). Conclusion: MD and PSD values measured by the Octopus and Humphrey perimetry instruments are based on measurements made under significantly different conditions, so the direct comparison of the indexes is not reliable. Nonetheless, empirically valid conversion formulas exist and can be used to compare the perimetric results for a patient tested with the two types of instrument.
Reproducibility of Nerve Fiber Layer Thickness Measurements Using Optical Coherence Tomography in Silicone Oil-Filled Eyes
Authors: Mastropasqua Leonardo , Carpineto Paolo , Ciancaglini Marco , Falconio Gennaro , Harris Alon
Published: April 2003

Purpose: To evaluate the reproducibility of nerve fiber layer (NFL) thickness measurements by optical coherence tomography (OCT) in individuals with silicone oil-filled eyes. Methods: Eighteen patients who had undergone pars plana vitrectomy and silicone oil tamponade for retinal detachment were enrolled in a prospective, case-controlled clinical study. Each patient underwent OCT measurement of NFL thickness. Five repetitions of a series of scans on five separate occasions within a 0.5-month period were performed. Each eye was scanned at two different nerve head programs [radius (R) = 1.5 and R = 1.73]. The contralateral healthy eye was used as control. For each option (R = 1.5 and R = 1.73) and region (superior, inferior, temporal, nasal and overall mean), variance components and intraclass correlation coefficients (ICCs) were determined using repeated-measures regression. In these models, NFL thickness, as measured by OCT, was considered to have three variance components: intersubject, intervisit (within subject, between dates), and intravisit (within subject, within date). The ICC (intersubject variance/total variance) was used as a measure of reliability. Results: The contralateral healthy eye provided a higher degree of reproducibility than the silicone oil-filled eye (p = 0.0001). Reproducibility was higher in a given eye on a given visit than from visit to visit. Reproducibility as measured by ICCs was as follows: R = 1.5, 0.54/0.30 (control eyes/silicone oil-filled eyes); R = 1.73, 0.51/0.30. Conclusions: Reproducibility results for OCT measurement of NFL thickness are different in healthy eyes and silicone oil-filled eyes. NFL thickness measurement is not reliable in silicone oil-filled eyes.
Eventual Error Caused by Dehydration with Pachometry
Authors: Sabetti L. , Renzetti A. , D’Alessandri L. , Balestrazzi E.
Published: April 2003

Among the possible variables responsible for systemic errors in the acquisition of pachometric measurements, the corneal hydration condition plays a determinant role. In the present study, the authors have investigated the importance of this condition with two different pachometers (Storz Corneoscan II and Allergan Humphrey), reproducing an experimental dehydrated condition. The main datum arising from the comparison of the measurements obtained is represented by the different time course of the value of the measurement in the two groups. In fact, confronting the medium initial superimposed thickness value in the two tables (521 vs. 520 µm) there is a substantial difference in the final examination. For the first group of 60 corneas, the thickness values appear almost identical in the different intervals of time (medium initial thickness 521 vs. 512 µm final thickness). For the group examined with the solid-point machine, a decreasing thickness equal to 7% was evidenced (520 vs. 482 µm) with a significant decrease in the corneal thickness after only 45 s.
Comparison of Hypotonic and Isotonic Solutions Containing Sodium Hyaluronate on the Symptomatic Treatment of Dry Eye Patients
Authors: Papa Vincenzo , Aragona Pasquale , Russo Simona , Di Bella Alessandro , Russo Pietro , Milazzo Giovanni
Published: April 2003

This study was designed to compare the efficacy of two artificial tears both containing hyaluronic acid but differing in their osmolarity. A multicentric double-masked, crossover clinical trial was performed in which 158 subjects were randomized to receive either hypotonic or isotonic artificial tears up to 6 times a day. Both treatments were effective in improving signs and symptoms to a similar extent. No adverse events were reported. It was concluded that hypotonic and isotonic eye drops are comparable for the symptomatic treatment of patients suffering from dry eye syndrome.
Coats’ Disease and Congenital Retinoschisis in a Single Eye: A Case Report and DNA Analysis
Authors: Berinstein Daniel M. , Hiraoka Miki , Trese Michael T. , Shastry Barkur S.
Published: April 2003

The clinical features of Coats’ disease and congenital retinoschisis (RS) are distinctly different. Therefore, finding changes consistent with Coats’ disease and congenital RS in a single eye is an unusual occurrence. The following report describes two cases with a Coats’ telangiectatic lesion in one region of the retina separated by normal retina and the presence of central and peripheral congenital RS. Molecular genetic analysis of the Norrie disease and RS genes failed to identify disease-causing or polymorphic mutations in either of the genes, suggesting that the above condition is clinically and genetically a different disorder. Further studies are needed to identify the genes responsible for the above disorder and associated ocular manifestations.
Effects of Isopropyl Unoprostone Ophthalmic Solution on Cultured Rabbit Corneal Epithelial Cells
Authors: Wang You-Dong , Kashiwagi Kenji , Chen Hai-Bo , Jin Ming , Ou Bo , Iizuka Yoko , Tanaka Yuko , Tsukahara Shigeo
Published: April 2003

Purpose: To investigate the effects of isopropyl unoprostone (referred to as unoprostone) ophthalmic solution on the barrier function of cultured rabbit corneal epithelium grown on permeable supports. Methods: Rabbit corneal epithelial cells cultured on collagen-coated filter inserts were administered one of the following for 30 min: unoprostone in vehicle solution (polysorbate 80), unoprostone in vehicle solution with a preservative (benzalkonium chloride), preservative only or vehicle only. For a control, no chemicals were added to the medium. After administration, the transepithelial electrical resistance (TER) measurement, a sensitive method by which to investigate the barrier function, and morphological observation using phase-contrast microscopy were performed before exposure and at 0.5, 1, 3, 6, 12, 24, 48 and 72 h after exposure. The transmission electron-microscopic observation was performed before and 72 h after exposure in all experimental conditions. Results: The cells exposed to unoprostone with the preservative showed a significant decrease in the TER, although no morphological changes were observed. The corneal epithelial cells exposed to unoprostone without preservative, the vehicle only or the preservative only did not show any differences from the control group at any measurements. Conclusion: The corneal barrier function is damaged by a combined solution of unoprostone and preservative, but not by a single solution of unoprostone, in vitro.
Safety of Ozonated Solution as an Antiseptic of the Ocular Surface prior to Ophthalmic Surgery
Authors: Kashiwagi Kenji , Saito Katsuya , Wang You-Dong , Takahashi Hiroshi , Ishijima Kiyotaka , Tsukahara Shigeo
Published: April 2003

Purpose: To evaluate the safety of an ozonated solution as an antiseptic of the ocular surface prior to ophthalmic surgery. Methods: In experiment 1, a primary culture of rabbit corneal epithelium was established. Then, 0, 4 and 10 ppm ozonated solution and 1.25% povidone-iodine, respectively, were applied to confluent cells on collagen-coated filter inserts (Millicell-CM®) for 10 min followed by replacement with fresh medium. The transepithelial electrical resistance (TER), which is a good indicator of cell barrier function, was sequentially measured for 30 min. In experiment 2, adult pigmented rabbit eyes were washed with 20 ml of 4 ppm ozonated solution, 1.25% povidone-iodine solution or saline. Slitlamp examinations were performed before and after washing. Results: In experiment 1, 4 ppm ozonated solution did not change the TER as compared with the control. 10 ppm ozonated solution and 1.25% povidone-iodine similarly reduced the TER values significantly as compared with those of the control and 4 ppm ozonated solution. In experiment 2, 4 ppm ozonated solution and saline showed mild superficial punctate keratitis (SPK) in 8.3% of eyes. However, 1.25% povidone-iodine resulted in mild SPK in 17% of eyes and moderate SPK in 25% of eyes. The prevalence of SPK between two groups was significantly different (p = 0.03). Conclusion: Ozonated solution may be safe and a useful antiseptic of the ocular surface prior to ophthalmic surgery.
A Morphometric Study of Age Changes in the Rat Optic Nerve
Authors: Cavallotti D. , Cavallotti C. , Pescosolido N. , Iannetti G.D. , Pacella E.
Published: April 2003

Age-related changes of the optic nerve fibres were studied in 3-month-old (young), 12-month-old (adult) and 24-month-old (aged) male Sprague-Dawley rats. The optic nerve was harvested with particular care from the intracranial portion. Cross sections from the optic nerve of animals of different age groups were stained with toluidine blue and examined under a light microscope at low and high magnification. Other sections were stained for the demonstration of glial cells using the method described by Holzer. A third group of sections were stained by the immunohistochemical method to detect glial fibrillary acidic protein, which is a marker for localising and characterising astrocytes. All these morphological results were subjected to the quantitative analysis of images and to statistical analysis of the values to identify significant morphometric data. Biochemical dosages of proteins were also performed on homogenised fragments of the optic nerve. Our results demonstrate that the following age-related changes can be observed: (1) an increase in meningeal membranes, (2) an increased number of astrocytes, (3) an increase in areal density of glial fibrillary acidic protein immunoreactivities, (4) an increased thickness of the entire optic nerve and an increased area of the nerve, (5) a decreased number of nerve fibres and (6) a decrease in the nerve fibre/meningeal membrane ratio from 3:1 to 1:1. Moreover, the amount of protein does not change with age. The rat optic nerve, therefore, appears sensitive to aging processes.
Spontaneous Resolution of Congenital Bilateral Brown’s Syndrome
Authors: Capasso Luigi , Torre Angelo , Gagliardi Vincenzo , Magli Adriano
Published: April 2003

We report a case of bilateral Brown’s syndrome in a 4-year-old girl. Forced duction testing confirmed the clinical diagnosis. After 7 months we observed a spontaneous resolution in the right eye. The problem in her left eye did not show any significant change over 36 months of follow-up. Various spontaneous resolutions in bilateral cases are reviewed.
Autochthon in Deutschland erworbene Ophthalmomyiasis externa: Kasuistik und Literaturübersicht
Authors: Weinand Frank S. , Bauer Christian
Published: April 2003

Infestation with larvae (maggots) is known as myiasis. Ophthalmomyiasis externa refers specifically to infestation that involves the lids and conjunctiva in man. Ophthalmomyiasis which originates from Germany is unusual, because the vector of the Oestrus ovis larvae is most prevalent in the warm climate of Mediterranean countries. The sheep nasal botfly (Oestrus ovis sp.) is responsible for most cases of external ophthalmomyiasis. This case report gives a detailed description of the larvae, their life cycle and an overview of infestations in Germany as well as the therapy of ophthalmomyiasis. Case Report: At the end of August 1999, a 28-year-old man attended the outpatient department of Giessen University Eye Clinic with a foreign body sensation in his left eye. He reported that something hit his left eye while he was climbing on his motorbike in the early evening hours. Shortly afterwards he had a foreign body sensation in his left eye. On history taking he reported no other ophthalmologic problems in the past. Slitlamp biomicroscopy revealed white, vivid, approximately 1.5-mm-long, light-sensitive maggots on the conjunctiva and under the upper lid. These were removed mechanically and the conjunctiva rinsed with saline. Local therapy was not applied. Conclusion: Infestation with larvae of O. ovis has to be considered not only in tourists from Mediterranean countries, but also in Germany in the late summer.
Leber’s Hereditary Optic Neuropathy Mutations in Korean Patients with Multiple Sclerosis
Authors: Hwang Jeong-Min , Chang Bong Leen , Park Sung Sup
Published: April 2003

Several different mitochondrial DNA (mtDNA) sites for mutations of Leber’s hereditary optic neuropathy (LHON) have been reported to be present in patients with multiple sclerosis (MS). To further study this association of LHON and MS in the Korean population, we tested 20 MS patients for the presence of mtDNA mutations at nucleotide (nt) 11778 in all 20 patients, and at nt 14484, nt 3460 and nt 15257 in 15, 12 and 12 patients, respectively. However, none of the MS patients exhibited any pathogenic LHON mtDNA mutations. In conclusion, we found no evidence for any association between MS and the LHON mutation in the Korean population.
Monocyte Chemotactic Protein-1 in the Vitreous of Patients with Proliferative Diabetic Retinopathy
Authors: Mitamura Yoshinori , Takeuchi Shinobu , Matsuda Akira , Tagawa Yoshitsugu , Mizue Yuka , Nishihira Jun
Published: April 2003

Purpose: To investigate the correlation between monocyte chemotactic protein-1 (MCP-1) levels in the vitreous and clinical findings in eyes with proliferative diabetic retinopathy (PDR). Methods: We assayed MCP-1 levels by ELISA in vitreous samples of 88 consecutive patients with PDR (52 eyes) and macular holes or idiopathic epimacular membrane (controls, 36 eyes). Results: The level of MCP-1 in the vitreous was 2,097.5 ± 1,099.4 pg/ml (mean ± SD) in PDR, and 504.3 ± 405.6 pg/ml in the controls. In PDR eyes, multivariate regression analysis revealed a significant association between MCP-1 levels in the vitreous and the degree of proliferative membrane, and a significant negative association between MCP-1 levels and the extent of preoperative retinal photocoagulation. Conclusion: The results suggest that MCP-1 may play a role in the development of the proliferative phase of PDR.
Effect of Ketanserin Administration on Intraocular Pressure
Authors: Tekat Düriye , Güler Cenap , Arici Mustafa Kemal , Topalkara Ayşen , Erdoğan Haydar
Published: April 2003

Purpose: We evaluated the effect of oral single-dose (20 mg) ketanserin on intraocular pressure (IOP) in normotensive and hypertensive eyes. Methods: This study included 15 healthy volunteers and 16 patients with ocular hypertension. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, IOP and pupil diameter were recorded at baseline and at 1-hour intervals for 6 h, in addition, tonographic outflow facility was studied at the third hour after the administration of placebo or an oral single dose of 20 mg ketanserin given in a randomized double-blind crossover fashion. The alternative treatment was applied a week later. Results: In both groups, oral single-dose (20 mg) ketanserin significantly lowered IOP and SBP (p < 0.01). No variation was observed in DBP, heart rate and pupil diameter (p >0.01). Moreover, after drug administration, the total outflow facility measured by conventional tonography increased in a statistically significant way (p < 0.01). Placebo did not induce any significant reduction in IOP and SBP in either group. Conclusion: The results showed that systemic ketanserin can be used in the treatment of glaucoma patients to reduce IOP.
Comparison of Blood Flow Velocities of the Extraocular Vessels in Patients with Pseudoexfoliation or Primary Open-Angle Glaucoma
Authors: Yüksel Nurşen , Karabaş V. Levent , Demirci Ali , Arslan Arzu , Altıntaş Özgül , Çağlar Yusuf
Published: April 2003

Purpose: To evaluate orbital blood flow velocities in patients with pseudoexfoliation glaucoma (PXG) or primary open-angle glaucoma (POAG). Methods: Blood flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries were evaluated by color Doppler imaging in 26 patients with PXG, 28 patients with POAG and 30 age-matched normal control subjects. The results were compared. Results: Compared to the control subjects, patients with PXG showed statistically significant decreases in the mean peak systolic and end-diastolic velocities and increased mean resistive indices in all vessels except for the ophthalmic artery mean peak systolic velocity (p < 0.05). Patients with POAG, when compared to the control subjects, showed statistically significant decreases in the mean end-diastolic velocities and increased mean resistive indices in all vessels measured (p < 0.05). No statistically significant differences were found in the mean blood flow parameters between POAG and PXG. Conclusion: Blood flow velocities of the retrobulbar vessels are decreased in patients with PXG. Reduced blood flow velocities may be secondary as well as contributory to exfoliative glaucomatous damage. Although there was no significant difference in the mean blood flow parameters between POAG and PXG, alterations of retrobulbar vessels might be associated with different pathogenic mechanisms of PXG.
R124C Mutation of the βIGH3 Gene Leads to Remarkable Phenotypic Variability in a Greek Four-Generation Family with Lattice Corneal Dystrophy Type 1
Authors: Hellenbroich Yorck , Tzivras Gerasimos , Neppert Birte , Schwinger Eberhard , Zühlke Christine
Published: April 2003

Five autosomal dominantly inherited corneal dystrophies are caused by missense mutations in the βIGH3 gene on chromosome 5q31. Here we describe the clinical features and the analysis of the βIGH3 gene in a Greek four-generation family with lattice corneal dystrophy type 1 (CDL1). Sequencing of the βIGH3 cDNA from an affected family member revealed the R124C mutation. More recent data indicate that this is probably a mutation hot spot in CDL1. We could not find a common haplotype with another CDL1 family with the R124C mutation demonstrating that this mutation occurs independently in different families. The clinical course of the disease showed a remarkable variability between the affected family members. To investigate a possible role between the phenotypic variability and apolipoprotein E (ApoE), which co-localises with amyloid deposits in CDL1, we determined the ApoE genotype of all family members. The resulting data revealed no association with the variable clinical course.
Effect of Terazosin on the Lipid Profile in Patients with Symptomatic Benign Prostatic Hyperplasia
Authors: Akbay Erdem , Bozlu Murat , Doruk Erdal , Akbay Esen , Çayan Selahittin , Ulusoy Ercüment
Published: April 2003

Introduction: To determine the changes in plasma lipid levels in symptomatic benign prostatic hyperplasia (BPH) patients receiving terazosin treatment. Materials and Methods: The study included 99 patients with BPH aged 44–74 years. The patients were divided into 3 groups: in group 1 (n = 25) with baseline total cholesterol levels of >220 mg/dl, terazosin 5 mg/day was used; in group 2 (n = 56) with basal total cholesterol levels of < 220 mg/dl, terazosin 5 mg/day was used, and group 3 (n = 18) did not use terazosin and was defined as the control group. Plasma levels of total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride were recorded, and the high-density lipoprotein to total cholesterol ratio was calculated at the beginning of the study and after 12 weeks. Results: The total cholesterol level decreased from the baseline level by 10.88% after 12 weeks (p < 0.05) in group 1. The decrease was observed in 22 of 25 patients (88%). In group 1, the mean plasma total cholesterol level decreased significantly (p < 0.05), but the decrease was not significant in group 2 and no change was observed in group 3. The mean plasma low-density lipoprotein level decreased significantly in group 1 (p < 0.05), but no change was observed in the other 2 groups. The mean plasma high-density lipoprotein level increased in group 1, whereas no change was observed in the other 2 groups. The mean plasma triglyceride level decreased significantly in groups 1 and 2 (p < 0.05), but no change was observed in group 3. The high-density lipoprotein to total cholesterol ratio increased significantly in group 1, but no change was observed in the other 2 groups. Conclusion: We suggest that terazosin may be a reasonable choice because of the beneficial effect on the lipid profile in older symptomatic BPH patients with a higher ratio of dyslipidemia.
Flow in Elliptical Vessels Calculated for a Physiological Waveform
Authors: Robertson Malcolm B. , Köhler Uwe , Hoskins Peter R. , Marshall Ian
Published: April 2003

Understanding the nature of pulsatile flow is an important issue in haemodynamics, especially the initiation and progression of vascular disease. The geometry of a non-circular vessel was idealised to an elliptical cross-section, and the dynamic properties of the flow were calculated for a physiological waveform. The Fourier harmonics for a common carotid waveform were determined, and the velocity profile and wall shear stress were calculated from the superposition of the individual contributions from each harmonic. The effects of ellipticity on the flow pattern were found to be significant. The velocity profile along the major axis of the elliptical cross-section developed a flattened peak, which widened as the vessel became more elliptical. Wall shear stress demonstrated an angular dependence in elliptical vessels, where the point of minimum shear stress was located at the end of the major axis. Comparison with a cylindrical vessel demonstrated a 3% decrease in peak wall shear stress (τ = 2.96, N·m–2) at the end of the major axis, and 10% in the mean wall shear stress (τ = 0.44 N· m–2), for an elliptical vessel (Ε = 0.8). The temporal average wall shear stress, which has been associated with atherogenic sites, also displayed a minimum at the end of the major axis that decreased with more elliptical cross-sections.
Biomechanical Properties of Porcine Cerebral Bridging Veins with Reference to the Zero-Stress State
Authors: Pang Qi , Lu Xiao , Gregersen Hans , von Oettingen Gorm , Astrup Jens
Published: April 2003

Passive mechanical and morphometric properties of porcine cerebral bridging veins were studied. Fifteen cerebral bridging veins were obtained from 7 pigs. The superior sagittal sinus, bridging veins and the meninges were excised and placed in aerated calcium-free Krebs solution. The outflow cuff segment is a narrow region at the junction of the cerebral bridging veins and superior sagittal sinus. The principal direction of collagen fibres was longitudinal in the bridging vein and circumferential in the cuff region. The diameter was smaller in the outflow cuff segment than in the cerebral bridging veins in the pressure range studied (0–23 mm Hg) whereas the thickness was highest in the outflow cuff segment (p < 0.01). The circumferential stress-strain analysis showed that the outflow cuff segment was extensible up to a strain of 0.25. At higher strains the outflow cuff segment was progressively stiffer than the cerebral bridging vein (p < 0.05). The longitudinal stress-strain relation for the cerebral bridging vein was shifted to the left compared to the outflow cuff segment (p < 0.05). When compared to the stress-strain properties in the circumferential direction, the outflow cuff segment was more extensible and the cerebral bridging vein stiffer in longitudinal direction (p < 0.05). The opening angle of the outflow cuff segment and the cerebral bridging vein was 115 ± 4 and 120 ± 4 (means ± SE) without statistical difference between the two regions. In conclusion the difference in biomechanical properties between the outflow cuff segment and the cerebral bridging vein was associated to their difference in histology and fibre arrangement. This indicates that the function of the outflow cuff segment is to act as a flow-limiting resistance to the outflow from the cerebral circulation.
Hirulog-Like Peptide Reduces Balloon Catheter Injury Induced Neointima Formation in Rat Carotid Artery without Increase in Bleeding Tendency
Authors: Xue Mengzhou , Ren Song , Welch Stephen , Shen Garry X.
Published: April 2003

Abstract: Vascular restenosis is one of the major concerns for the management of coronary artery disease using therapeutic vascular procedures. Treatments with thrombin-specific inhibitors, hirudin or hirulog-1, reduced ischemic events in coronary artery disease patients. Early started and prolonged infusions of these thrombin inhibitors partially prevented balloon catheter injury induced restenosis or neointima formation in experimental animal models, but increased the bleeding tendency. Hirulog-like peptide (HLP) was rationally designed to enhance the inhibition of the binding of thrombin to its receptor with less interruption of coagulation activity in comparison to hirulog-1. A single infusion of HLP for 4 h started 0.5 h before balloon catheter injury reduced neointima formation by 36% in rat carotid artery compared to vehicle controls. Tail bleeding time and activated partial thromboplastin time during HLP infusion were not significantly different from vehicle controls, but were significantly shorter than during heparin or hirulog-1 infusion. HLP treatment attenuated the expression of platelet-derived growth factor in the neointima of injured arteries. HLP also inhibited thrombin-induced thymidine incorporation in cultured baboon aortic smooth muscle cells. The findings suggest that HLP may substantially inhibit balloon catheter injury induced neointima formation without noticeable increase in bleeding tendency in rats. The inhibition by HLP of the expression of platelet-derived growth factor and of the smooth muscle cell proliferation in the vascular wall potentially contributes to the preventive effect of the new thrombin inhibitor on injury-induced neointima formation in the vascular wall.
Oleate Oxidation and Mitochondrial Substrate Selection in Vascular Smooth Muscle
Authors: Allen Tara J. , Hardin Christopher D.
Published: April 2003

The purpose of this study was to determine the contribution of long-chain fatty acids relative to other mitochondrial substrates in active vascular smooth muscle (VSM). Hog carotid arteries were isometrically contracted in physiological saline solution containing 0.71 mM U-13C-oleic acid (bound to albumin at a ratio of 6.8:1), 5 mM 1-13C-glucose and 1 mM acetate in the presence or absence of 5 mM carnitine for 6 h at 37°C. Substrate oxidation was determined using 13C-isotopomer analysis of glutamate. Although oxidation of oleic acid could not be measured at physiological concentrations [0.5 mM (1:1)], oleic acid oxidation was approximately 5% of the total substrates oxidized at the higher concentration examined. Although insignificant, carnitine increased oleic acid oxidation to approximately 8%, and resulted in a decrease in endogenous lipid oxidation, which was 2–12% of the total substrates oxidized. Oxidation of glucose and acetate did not significantly change due to the inclusion of oleic acid in the incubation solutions. Therefore, we conclude that exogenous long-chain fatty acids are minor contributors to substrate oxidation (approximately 5%) in VSM compared to other mitochondrial substrates, such as glucose and acetate, which account for approximately 80% of the substrates oxidized by VSM.
Increased Store-Operated Ca2+ Entry into Contractile Vascular Smooth Muscle following Organ Culture
Authors: Dreja Karl , Bergdahl Andreas , Hellstrand Per
Published: April 2003

Ca2+ inflow via store-operated Ca2+ channels was investigated in rings of rat tail and basilar arteries kept in serum-free organ culture, which is known to preserve the contractility of the vascular smooth muscle. After culture for 3–4 days, Ca2+ release from intracellular stores in response to caffeine (20 mM) was augmented 2- to 4-fold. Following depletion of intracellular Ca2+ stores by caffeine and thapsigargin (10 µM), addition of Ca2+ (2.5 mM) caused an increase in the intracellular Ca2+ concentration which was 2–3 times greater in cultured than in freshly dissected rings, and was not affected by verapamil (10 µM). In contrast, L-type Ca2+ channel currents were decreased by 20% after culture. While freshly dissected rings developed no or very little force in response to the addition of Ca2+ after store depletion, cultured rings developed 42% (tail artery) and 60% (basilar artery) of the force of high-K+-induced contractions. These contractions in cultured vessels were insensitive to verapamil but could be completely relaxed by SKF-96365 (30 µM). Store depletion by caffeine increased the Mn2+ quench rate 3- to 4-fold in freshly dissected as well as cultured tail artery, while there was no increase in freshly dissected basilar artery, but a 3-fold increase in cultured basilar artery. Uptake of Ca2+ into intracellular stores was twice as rapid in cultured as in freshly dissected tail artery. This study shows that organ culture of vascular smooth muscle tissue causes changes in Ca2+ handling, resembling the pattern seen in dedifferentiating smooth muscle cells in culture, although contractile properties are maintained.
Monocyte Chemotactic Protein 1 Amplifies Serotonin-Induced Vascular Smooth Muscle Cell Proliferation
Authors: Watanabe Takuya , Pakala Rajbabu , Katagiri Takashi , Benedict Claude R.
Published: April 2003

Monocyte chemotactic protein 1 (MCP-1), which is synthesized by vascular cells, is a chemoattractant for monocytes and has been implicated in a wide range of acute and chronic inflammatory processes characterized by monocyte infiltration, including atherosclerosis. However, it is unclear whether MCP-1 is able to modulate vascular smooth muscle cell (VSMC) proliferation. We assessed the effect of MCP-1 on VSMC proliferation and its interaction with serotonin (5-HT), a mitogen for VSMCs. Growth-arrested VSMCs were stimulated with different concentrations of MCP-1 (25–200 ng/ml) and 5-HT (5 and 50 µM) in serum-free medium. DNA synthesis in VSMCs was measured by [3H]thymidine incorporation. 5-HT at concentrations of 5 and 50 µM significantly stimulated DNA synthesis by 1.8- and 2.1-fold over the control value, respectively (p < 0.0001). However, MCP-1 at the concentrations tested did not have any significant effect on DNA synthesis. Even though MCP-1 (50 ng/ml) by itself is not mitogenic, when added to 5-HT, it significantly amplified the mitogenic effect of 5-HT compared with that of 5-HT alone (p < 0.0001). The 5-HT2A receptor antagonist sarpogrelate (10 µM) and its major metabolite M-1 (0.1 µM), pertussis toxin (10 ng/ml), Src family protein tyrosine kinase (PTK) inhibitor PP2 (1 µM), protein kinase C (PKC) inhibitor Ro31-8220 (0.1 µM) and mitogen-activated protein kinase (MAPK) kinase inhibitor PD098059 (10 µM) significantly inhibited the mitogenic effect of 5-HT and its interaction with MCP-1. Anti-MCP-1 antibody (2 µg/ml) and the Janus kinase 2 (JAK2) inhibitor AG490 (10 µM) significantly inhibited the interaction of MCP-1 with 5-HT. Further, the amplified mitogenic effect of 5-HT with MCP-1 was completely reversed by the combined use of sarpogrelate with anti-MCP-1 antibody. Our results suggest that MCP-1 amplifies the mitogenic effect of 5-HT on VSMCs. The mitogenic effect of 5-HT may be mediated by the G protein-Src family PTK-PKC-MAPK pathway. The activation of the JAK2/signal transducer and activator of transcription 3 pathway by MCP-1 in addition to the MAPK pathway by 5-HT may explain the potentiating effect of MCP-1 on 5-HT-induced mitogenesis.
The Interaction between the Renin-Angiotensin System and Vascular Endothelial Growth Factor in the Pathogenesis of Retinal Neovascularization in Diabetes
Authors: Wilkinson-Berka Jennifer L. , Kelly Darren J. , Gilbert Richard E.
Published: April 2003

Despite the use of laser photocoagulation and knowledge of the beneficial effects of good glycaemic control, visual loss due to diabetic retinopathy remains the commonest cause of blindness in the working population. This visual loss is principally the result of proliferative diabetic retinopathy and macular oedema. The processes by which diabetes mellitus results in retinopathy are incompletely understood, but recent evidence has suggested a pathogenetic role for the renin-angiotensin system (RAS) and vascular endothelial growth factor (VEGF) in the eye in response to chronic hyperglycaemia. This review will explore evidence of a local RAS in the eye, the involvement of VEGF in diabetic retinopathy and the interaction between the RAS and VEGF in the pathogenesis of retinal neovascularization.
On the Role of Clinical Genetics in 2010
Authors: Schmidtke Jörg
Published: April 2003

While only the speciality of clinical genetics has developed the skills and attitudes to comprehensively fulfil the requirements of a genetic service system, it is only one of several disciplines involved in genetic service provision. The future of clinical genetics will depend on its ability to maintain educative competence regarding genetics in medicine whilst becoming a partner in a multidisciplinary service team. Furthermore, the expertise of clinical geneticists will play an important role in the regulation of the genetic test market.
Familial Hypercholesterolaemia: Taking Advantage of a Founder Effect for Early Diagnosis and Treatment
Authors: Miltiadous George , Cariolou Marios A. , Elisaf Moses
Published: April 2003

Objective: To characterise the mutations in the low-density lipoprotein (LDL) receptor gene in patients with heterozygous familial hypercholesterolaemia (FH) living in northwestern Greece and to determine the geographical distribution of these mutations if any. Methods: DNA analysis for the LDL receptor gene was performed (using restriction enzyme method or direct sequencing) in unrelated patients attending our lipid clinic with a clinical diagnosis of heterozygous FH. Results: The 1775G→A LDL receptor gene mutation is the most common mutation causing FH in our area and is restricted to a mountainous area called Tzoumerka, which shows a founder effect. Conclusion: The screening of the population in Tzoumerka area is strongly recommended for the detection of new FH patients. Furthermore, patients originating from Tzoumerka and attending other lipid clinics with a clinical diagnosis of FH could have their DNA tested for the above mutation.
A Review on Blood Pressure and Ischaemic White Matter Lesions
Authors: Skoog Ingmar
Published: April 2003

Hypertension or high blood pressure is constantly reported to be the main risk factors for ischaemic white matter lesions (WMLs). These lesions show the histopathological picture of diffuse demyelination and moderate loss of axons in subcortical structures. The main hypothesis regarding the association between high blood pressure and ischaemic WMLs is that long-standing hypertension causes lipohyalinosis of the media and thickening of the vessel walls with narrowing of the lumen of the small perforating arteries and arterioles which nourish the deep white matter. Episodes of hypotension may then lead to hypoperfusion and hypoxia-ischaemia in the white matter. In line with this, low blood pressure has also been reported to be a risk factor for WMLs. However, also other pathogenetic mechanisms may be involved. Hypertension may cause disturbances in the blood-brain barrier, which may cause lesions in the white matter by cerebral oedema, by activation of astrocytes or by destructive enzymes or other poisons which pass through the damaged vessel walls. The renin-angiotensin system is an example of a system that may be involved in the pathogenesis of both hypertension and arteriosclerosis. Its effector peptide angiotensin II has several blood-pressure-increasing effects, such as direct vasoconstriction and activation of the sympathetic nervous system. It also promotes hyperplasia and hypertrophy in vascular smooth muscle cells. Recently an association between hypertension and Alzheimer’s disease has been reported. It is not clear whether this may be the reason for the common occurrence of WMLs in cases of late-onset Alzheimer’s disease, as Alzheimer’s disease may also cause lesions in the cerebral microvasculature. The association between WMLs and hypertension may thus be mediated through several different pathogenetic pathways.
The Clinical Trial Protocol of the Metrifonate in ALzheimer’s Trial (MALT)
Authors: McKeith Ian G.
Published: April 2003

The promising results of early trials in Alzheimer’s disease with the acetylcholinesterase inhibitor metrifonate prompted initiation of the Metrifonate in ALzheimer’s Trial (MALT). MALT is an international, randomized, double-blind, placebo-controlled, parallel-group study which was designed to determine, over a 26-week period, the efficacy, tolerability and safety of two doses of metrifonate in patients with probable Alzheimer’s disease. A total of 605 patients were randomized to receive either a daily dose of oral metrifonate 40/50 mg (n = 200, by body weight <65 kg/≧65 kg) or metrifonate 60/80 mg (n = 197, by body weight <65 kg/≧65 kg). Patients were assessed in the key symptom domains of Alzheimer’s disease, i.e. cognition, behavioural and psychiatric disturbances, activities of daily living and global function. In summary, administration of metrifonate for 26 weeks to the intent-to-treat population significantly benefited cognitive performance, global function and certain aspects of behaviour and functional ability compared with placebo. These efficacy results were associated with high levels of acetylcholinesterase inhibition and a good safety and tolerability profile. The protocol of MALT is discussed here. Full results of the study will be available in a separate publication.
The Pharmacological Basis for Metrifonate’s Favourable Tolerability in the Treatment of Alzheimer’s Disease
Authors: Schmidt Bernard H. , Heinig Roland
Published: April 2003

Metrifonate, through its pharmacologically active metabolite 2,2-dichlorovinyl dimethylphosphate (DDVP), is a long-acting cholinesterase inhibitor for the symptomatic treatment of mild-to-moderate Alzheimer’s disease. Clinical studies with Alzheimer patients have demonstrated the favourable safety and tolerability profile of this drug. Metrifonate, at therapeutic doses for Alzheimer’s disease, achieves high levels of cholinesterase inhibition, i.e. ≧70%, without the need for dose escalation. This is a consequence of the low rate of fluctuation of enzyme activity during therapy with metrifonate. This, in turn, is due to the protracted hydrolytic transformation of metrifonate into DDVP, the resulting smooth onset of cholinesterase inhibition, and the subsequent long duration of action which far outlasts the presence of the active drug in the body. Both metrifonate and DDVP are rapidly metabolized and eliminated from the body. Further, their metabolism does not involve the cytochrome P450 system and both compounds show low plasma protein binding. These pharmacokinetic features account, at least in part, for the favourable safety and tolerability profile of metrifonate as they suggest a minimal risk of drug-drug interactions with other likely co-medications in the long-term therapy of Alzheimer patients.
Clinical Subtypes of Alzheimer’s Disease
Authors: Petersen R.C.
Published: April 2003

Alzheimer''s disease (AD) can present as a variety of clinical profiles. Although the most common presentation is that of a progressive amnestic disorder with subsequent involvement of other cognitive functions and personality alterations, there are numerous other clinical profiles. AD can present as a focal cortical degenerative syndrome with the clinical features dependent on the regions of the brain involved. Some of these syndromes include disturbances of language, visuospatial skills, attentional functions, executive processes and praxis. The neuropathological substrate of these disorders is variable and can include AD. Recently, the Lewy body variant of AD has been described. Finally, other modifying features that affect the progression of AD, such as extrapyramidal symptoms and myoclonus, are also discussed. Although the progressive amnestic form of AD is the most common presentation, other variations on the clinical syndrome can be important to identify because they may have implications for prognosis and treatment.
Genetic Association between Alzheimer Disease and the Alpha-Synuclein Gene
Authors: Matsubara Miho , Yamagata Hidehisa , Kamino Kouzin , Nomura Takuo , Kohara Katsuhiko , Kondo Ikuko , Miki Tetsuro
Published: April 2003

α-Synuclein has been isolated as a component of amyloid in addition to the major Aβ peptide in Alzheimer disease (AD). However, there are conflicting reports regarding the association of α-synuclein gene polymorphism with AD. Using a novel and common polymorphism in intron 3, we examined the relationship between AD and α-synuclein and apolipoprotein E (ApoE) genes in 183 Japanese AD patients and 210 controls. Carriers of the α-synuclein deletion (D) allele had a 2.2-fold increased risk of developing AD than noncarriers in women. The odds ratio for the ApoE Ε4 and the α-synuclein D allele was 11.4 in women. The results showed that the α-synuclein gene is associated with sporadic AD in women, independent of ApoE Ε4 status.
Interrater Reliability of the Modified Jadad Quality Scale for Systematic Reviews of Alzheimer’s Disease Drug Trials
Authors: Oremus Mark , Wolfson Christina , Perrault Anne , Demers Louise , Momoli Franco , Moride Yola
Published: April 2003

Drug therapies for Alzheimer’s disease (AD) have been evaluated in clinical trials over the past 2 decades. Systematic reviews of AD drug trials can shed more light on the efficacy of pharmaceutical interventions. The modified Jadad scale can be used to assess the quality of trial reports that are candidates for inclusion in these systematic reviews. The interrater reliability of the modified Jadad scale was examined during such a review. Three blinded reviewers rated the quality of 42 AD drug trial reports: the intraclass correlation coefficient was 0.90. The modified Jadad scale appears to be a useful tool for AD research because of the very good interrater reliability. Also, it is composed of items that are well suited to the specific disease characteristics of AD. Further research should focus on the validity of this instrument.
The Cerebrospinal Fluid Levels of Tau, Growth-Associated Protein-43 and Soluble Amyloid Precursor Protein Correlate in Alzheimer’s Disease, Reflecting a Common Pathophysiological Process
Authors: Sjögren Magnus , Davidsson Pia , Gottfries Johan , Vanderstichele Hugo , Edman Åke , Vanmechelen Eugeen , Wallin Anders , Blennow Kaj
Published: April 2003

Cerebrospinal fluid (CSF) levels of tau (total tau), growth-associated protein-43 (GAP-43), soluble amyloid precursor protein (sAPP; i.e. total sAPP), and β-amyloid42 (Aβ42) were studied in patients with frontotemporal dementia (FTD; n = 14), Alzheimer’s disease (AD; n = 47) and vascular dementia (VAD; n = 16), and in age-matched controls (n = 12). CSF-tau was increased in AD compared to controls and FTD (p < 0.001 for both). CSF-GAP-43 was increased in AD compared to controls (p < 0.05), and both CSF-GAP-43 and CSF-sAPP were increased in AD compared to FTD (p < 0.01). Positive and highly significant correlations were found between CSF-tau and CSF-GAP-43 in all groups and between CSF-tau, CSF-GAP-43 and CSF-sAPP in AD. The correlations found may reflect a common pathophysiologic process such as axonal degeneration.
Constructional Apraxia in Alzheimer’s Disease: Association with Occipital Lobe Pathology and Accelerated Cognitive Decline
Authors: Smith M.Z. , Esiri M.M. , Barnetson L. , King E. , Nagy Zs.
Published: April 2003

The functional impact and progression of occipital lobe pathology in sporadic late onset Alzheimer’s disease (AD) is barely explored. It is accepted that the primary and association visual areas are affected relatively late, in the neocortical stages of AD. We analysed 60 prospectively assessed AD patients in whom global cognitive deterioration and constructional apraxia were evaluated longitudinally using the CAMDEX. Radioactive immunohistochemistry was used to assess the amount of AD-related pathology in Brodmann areas 18 and 17. Braak staging of each case was also carried out. This study showed that in AD patients constructional apraxia is associated with higher expression of hyperphosphorylated tau. Additionally our findings indicate that early constructional apraxia is a predictor of accelerated cognitive decline in AD.
Tolerance of Topical Retinaldehyde in Humans
Authors: Sachsenberg-Studer E.M.
Published: April 2003

Background: Retinaldehyde (RAL) has been used as a topical agent in many countries since 1994. Aim: To review current data on the tolerance of retinaldehyde and to report the results of a long-term pilot study. Methods: Data from published and on-file studies have been compiled. Forty-five patients who had applied RAL on the face for 12–89 months were specifically examined for side-effects. Results: Studies in humans demonstrated an excellent tolerance of topical RAL on human skin. It was much better tolerated than retinoic acid and could be used even on sensitive facial skin. It does not have phototoxic or photo-allergic properties. No side-effects were associated with long-term use. Conclusion: Current data indicate a good topical tolerance of RAL in humans.
Importance of Bile Reflux in Barrett’s Esophagus
Authors: Richter Joel E.
Published: April 2003

Barrett’s esophagus (BE) is an acquired condition in which the squamous epithelial lining of the lower esophagus is replaced by a columnar epithelium due to chronic gastroesophageal reflux. The role of acid and bile in the development of esophageal mucosal injury and the formation of BE is controversial. Acid and pepsin are unquestionably important in causing mucosal damage and BE formation in both animal models and humans. Animal studies suggest the potential for synergistic damage from conjugated bile acids and gastric acid, as well as from unconjugated bile acids and trypsin in more neutral pH settings. Evidence of the involvement of bile and its constituents in humans has been less conclusive; however, the advent of better technology to detect bile reflux is beginning to clarify the role of these constituents. Human studies show that the reflux of bile parallels acid reflux and increases with the severity of gastroesophageal reflux disease, being most marked in BE. However, recent ex vivo studies suggest that pulses of acid reflux may be more important than bile salts in the development of dysplasia or adenocarcinoma in Barrett’s epithelium. Nevertheless, antireflux surgery and aggressive acid suppression with proton pump inhibitors will decrease both acid and bile refluxes, and eliminate the synergism between these two duodenogastric constituents.