bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Ultrasonography in the Diagnosis of Orbital Lymphangiomas
Authors: Parentin Fulvio , Borzaghini Lucio , Perissutti Paolo
Published: April 2003

Orbital lymphangiomas are benign hamartomatous tumours usually diagnosed in early childhood. In contrast with the benign histology, these lesions have a locally aggressive nature. They may enlarge slowly, producing mild proptosis; nevertheless intrinsic haemorrhage can occur, producing a mass effect and leading to intractable, painful, progressive proptosis, and compressive optic neuropathy. A conservative approach is advisable for several reasons: complete resection is difficult because these lesions, unlike haemangiomas, are not encapsulated, do not respect anatomic boundaries, tend to penetrate into normal structures, and can bleed profusely during surgery. For these reasons, an early diagnosis is important. On this subject, ultrasonography appears to be the first-choice diagnostic test, because of its sensitivity and simplicity, particularly in childhood; therefore we recommend to always perform this test in the presence of orbital vascular lesion.
Transscleral Diode Laser Photocoagulation in Refractory Glaucoma
Authors: Pucci Vincenzo , Marchini Giorgio , Pedrotti Emilio , Morselli Simonetta , Bonomi Luciano
Published: April 2003

Background and Objective: Patients with glaucoma refractory to medical or surgical treatment are difficult to treat. The aim of this study was to evaluate the effect of contact transscleral diode laser cyclophotocoagulation (DLPC) on these patients’ intra-ocular pressure (IOP) and visual acuity. Patients and Methods: 37 eyes of 36 patients who suffered from refractory glaucoma and who had undergone DLPC, were followed at the Eye Clinic of Verona University for an average of 14 ± 4 months. The average age was 54 ± 26 years. IOP, visual acuity and ocular complications were analysed. Results: A total of 71 treatments were given. More than 1 treatment was given in 22 eyes (59%). The mean pretreatment IOP was 33.1 ± 3.3 mm Hg. At the last follow-up, the mean IOP was 21 ± 1.6 mm Hg. Mean total medications were reduced from 4.4 ± 0.5 to 2.4 ± 0.3. No serious complications occurred in 71 treatments. Visual acuity remained stable in 25 eyes (67.5%), improved in 6 eyes (16.2%) and decreased in 6 eyes (16.2%). Conclusions: DLPC is effective in lowering IOP in eyes with refractory glaucoma. It also serves to reduce the number of antiglaucoma medications. This procedure is relatively safe. Nevertheless, multiple DLPC applications may be needed.
The Biocompatibility of Silicone, Fluorosilicone and Perfluorocarbon Liquids as Vitreous Tamponades
Authors: Versura Piera , Cellini Mauro , Torreggiani Alberto , Bernabini Benedetta , Rossi Annalisa , Moretti Marco , Caramazza Roberto
Published: April 2003

Purpose: To investigate the interactions occurring at the interface between some currently used vitreous tamponading substances and the ocular tissues, in an early follow-up after surgery. Methods: Adult albino rabbit eyes underwent vitrectomy and were injected intravitreally with silicone oils at 1,000 or 3,000 cSt, fluorosilicone oil and perfluorodecalin. Different morphological techniques (light microscopy, scanning and electron microscopy, immunohistochemistry) were applied. Results: All the tested materials, although non-toxic, penetrate the ocular tissues also at the anterior segment level, and in the long-term follow-up this can yield functional impairment. No massive inflammation has been detected in the zones in contact with the materials, but immunoglobulins and complement fractions are anyway present in the stroma of various tissues and around the droplets of emulsified materials, suggesting a local immune reaction. Conclusions: Data from this study confirmed that a permanent vitreous substitute, showing a perfect biocompatibility, still does not exist. The indication to remove the tamponading substance within 2 months after the surgery emerges from this investigation, confirming previous studies. Despite some negative features, silicone oil still appears the most biocompatible material for vitreous replacement.
Cyclosporine Effects on Clinical Findings and Impression Cytology Specimens in Severe Vernal Keratoconjunctivitis
Authors: Avunduk Avni Murat , Avunduk Mustafa Cihat , Erdöl Hidayet , Kapicioglu Zerrin , Akyol Nurettin
Published: April 2003

Purpose: To investigate the possible effects of topical cyclosporine eye drops 2% (CsA) on conjunctival immune cells obtained by impression cytology technique and to determine the clinical relevance of this effect if present. Methods: Ten consecutive patients with severe, resistant, and active vernal keratoconjunctivitis (VKC) were included in this study. All of them were treated with 2% of topical CsA drops. Symptom and clinical scores and conjunctival impression cytology specimens were obtained both before and following treatment. Impression cytology specimens were stained with anti-CD8+, CD4+, CD45RA+, and CD23+ antibodies and the percentages of positive cells were counted. The results were compared and correlation analyses were performed between clinical and laboratory data. Results: Significant reductions were observed with respect to the percentages of CD4+ and CD23+ cells in the conjunctival impression cytology specimens and clinical and symptom scores following treatment with topical CsA, while no change occurred in the percentages of CD8+ and CD45RA+ cells. The percentages of CD4+ and CD23+ cells showed good correlations with symptom and clinical scores. Conclusion: Topical CsA treatment is a very effective alternative in severe VKC cases in clinical ground and clinical efficacy of topical CsA treatment in severe, resistant VKC cases can be (at least partly) related to reduction of the CD23+ and CD4+ cell populations on the conjunctival surface.
Orbital Epithelial Cyst Derived from the Lacrimal Sac
Authors: Hsu Huan-Chen , Lin Sue-Ann
Published: April 2003

We describe a 32-year-old female who presented with a painless, moderately hard mass in the left inferior medial canthal region which had been present for about 6 years. She suffered from epiphora in the left eye in that time. The nasolacrimal system was completely patent on irrigation. Computed tomography showed a nodular mass with a diameter measuring about 25 mm located over the upper portion of the left lacrimal sac. The lesion was found to be a cyst located separately with close proximity to the lacrimal sac via anterior orbitotomy. Histopathologic examination revealed a cystic cavity lined by columnar to cuboidal epithelium consistent with a cyst derived from lacrimal sac epithelium. The patient has remained free of symptoms with a patent lacrimal system during the follow-up period of 1 year, without recurrence of the lesion. Orbital cysts of lacrimal sac derivation should be considered in the diagnosis of medial orbital tumors. Careful evaluation clinically with imaging studies and planning surgery constituted adequate therapy in this case.
Intraocular Hemangiopericytoma
Authors: Shimura Masahiko , Suzuki Keiko , Fuse Nobuo , Yoshida Madoka , Saiki Yuriko , Ohtani Haruo , Tamai Makoto
Published: April 2003

A 55-year-old man presented with a smoothly elevated solid choroidal mass with choroidal detachment in the temporal region of the left eye. Both fluorescein and indocyanine green angiography suggested a vascularized lesion such as an angioma. However, radiographic examination revealed a solid, circumscribed, dome-shaped mass. During a 3-month observation, the mass gradually enlarged and invaded the iris. The possibility of malignant melanoma could not be ruled out. Due to rapid and continued growth of the tumor, the eye was enucleated. Histopathologic examination revealed proliferation of spindle-shaped cells surrounding reticulin-positive vessels, which is characteristic of hemangiopericytoma. To our knowledge, this is only the fourth reported case of intraocular hemangiopericytoma and the first diagnosed in a male patient.
Interferon β Affects Retinal Pigment Epithelial Cell Proliferation via Protein Kinase C Pathways
Authors: Qiao Hong , Sakamoto Taiji , Hinton David R. , Gopalakrishna Rayudu , Ishibashi Tatsuro , Ryan Stephen J. , Inomata Hajime
Published: April 2003

Background: The aim of this study is to see the effect of interferon β (IFN-β) on cell proliferation and the protein kinase C (PKC) signaling pathway. Methods: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-β, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-β were assessed by 3H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-β and calphostin C was also measured.Results: IFN-β inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and 3H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-β had no inhibitory or stimulatory effect on 3H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-β exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. Conclusion: IFN-β inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.
Calcium Oxalate Crystal Attachment to Cultured Rat Kidney Epithelial Cell, NRK-52E
Authors: Yasui Takahiro , Fujita Keiji , Tozawa Keiichi , Asai Kiyofumi , Soji Tsuyoshi , Kato Taiji , Kohri Kenjiro
Published: April 2003

Madin-Darby canine kidney (MDCK) cells have been used in research on crystal adhesion to epithelial cells. Recently, matrix proteins were identified, and studies of the genes and proteins expressed in renal epithelial cells have become active. The present study confirms the usefulness of the NRK-52E cell line, derived from the rat, in the study of attachment with calcium oxalate crystals. The calcium oxalate crystal suspension was distributed on top of the cells. After incubation, the monolayers were rinsed to remove non-associated crystals. After fixation, the association of crystals and NRK-52E cells was visualized using scanning electron microscopy. Calcium oxalate crystals were attached to the surface of NRK-52E cells. Under high magnification, many of the microvilli of the cells had elongated towards the crystals, and microvilli projections appeared to catch the crystals. The NRK-52E cell line is useful in the study of attachment between crystals and urinary epithelial cells in the kidney, especially for the regulation and analysis of genes and proteins.
Adult Testicular Pure Yolk Sac Tumor
Authors: Medica Mauro , Germinale Francesco , Giglio Matteo , Stubinski Robert , Campodonico Fabio , Raggio Matteo , Carmignani Giorgio
Published: April 2003

Here we describe the clinical, ultrasonographic and histological features of a rare pure adult yolk sac tumor detected in the right testis of a 44-year-old male. Due to the rarity of this neoplasm (less than 10 cases have been reported), there is no unanimous consensus for therapy following inguinal orchiectomy. We believe that nerve-sparing retroperitoneal lymph node dissection could be potentially curative and useful for future interpretations of this tumor’s potential evolution.
Primary Lymphoma of the Epididymis
Authors: Novella G. , Porcaro A.B. , Righetti R. , Cavalleri S. , Beltrami P. , Ficarra V. , Brunelli M. , Martignoni G. , Malossini G. , Tallarigo C.
Published: April 2003

Objective: To report an extremely rare clinical pathological observation of a case of primary lymphoma of the epididymis, without testicular or systemic involvement, and to update the relevant literature. Materials and Methods: A 25-year-old white male patient complaining of right scrotal pain was referred to our department. Clinical examination detected a hard painful mass at the right epididymal head. Epididymitis was diagonsed and conservative therapy with antibiotics and anti-inflammatory drugs was given. After 2 months of therapy the patient was admitted to our department because a tumor was suspected. Tumor markers were normal. Right scrotal exploration was performed through a standard inguinal incision. The epididymal head was completely replaced by a hard white mass. Fresh frozen sections indicated a malignant tumor. Right radical orchiectomy was performed. Results: High-grade primary epididymal non-Hodgkin’s lymphoma with diffuse large cells (group G according to the Working Fromulation) was diagnosed. Clinical pathological staging detected stage IE (extranodal) primary epididymal lymphoma. The patient was referred to the Hematologic Unit for combined chemotherapy, according to the VACOP-B protocol. After an 18-month follow-up the patient is well and disease free. Conclusions: When an epididymal mass does not benefit from medical treatment, scrotal exploration and fresh frozen sections of the lesion should be done. The possible bilateral involvement by primary epididymal lymphoma has to be kept in mind. Radical orchiectomy is the treatment of choice for primary lymphoma of the epididymis. Adjuvant chemotherapy is indicated in high-grade malignant lymphoma. Prognostic parameters of the disease may be the grade of malignancy and the size of the tumor.
Clear Cell Adenocarcinoma of the Male Urethra in Association with So-Called Nephrogenic Metaplasia
Authors: Seseke Florian , Zöller Gerhard , Kunze Ekkehard
Published: April 2003

A clear cell adenocarcinoma of the urethra associated with so-called nephrogenic metaplasia occurring in a 57-year-old male patient is presented. Ten months following total urethrectomy, multiple pulmonary metastases had developed. The patient died 2.5 years after surgery. The possible histogenesis of clear cell adenocarcinoma of the lower urinary tract – reported to develop in the male urethra only in a very few cases – is reviewed briefly. We favor an origin from preexisting nephrogenic metaplasia as one of the possible histogenetic pathways.
Priapism Associated with Intracavernosal Injection of Cocaine
Authors: Mireku-Boateng A.O. , Tasie Bert
Published: April 2003

We describe a case of priapism associated with intracavernosal injection of cocaine and our treatment approach and discuss the pathophysiologic mechanisms of cocaine-induced priapism and offer a physiologic approach to its management.
Incidental Splenectomy during Left Radical Nephrectomy: Reasons and Ways to Avoid It
Authors: Carmignani Giorgio , Traverso Paolo , Corbu Carlo
Published: April 2003

Introduction: Left radical nephrectomy is the second most common cause of incidental splenectomy during transabdominal oncological surgery in the upper left quadrant of the abdomen. The potential sequelae of splenic ablation are often underestimated and generally no systematic planned efforts have been undertaken to avoid a splenic injury. Material and Methods: We evaluated the incidence of iatrogenic splenectomy in 333 cases of left radical nephrectomy for renal cancer performed at our institute between 1970 and 1999. Two slightly different surgical techniques were adopted and after 1995 particular attention was paid to the possible causes of intraoperative splenic injury and how to avoid it. In the first group of patients (1970–1994) an anterolateral xipho-umbilical-subcostal approach was used, and in the second group (1995–1999) a cruciate ‘Mercedes-like’ incision was always adopted. Results: The incidence of iatrogenic splenectomy in the first group of patients was 13.2%, and only 2.6% in the second group. The mortality rate in the first group of patients was 6%; no mortality has been recorded in the second group. Postoperative infections averaged 12.1% in the first group and 11.6% in the second, without any difference between the two groups. However, if we consider the incidence of postoperative infections in splenectomy cases, the incidence reaches 24.2% in the first group versus no cases in the second. Conclusions: Incidental splenectomy is a potentially severe complication of transabdominal left radical nephrectomy and is often considered a price that has to be paid, particularly in cases of large tumoral masses. A more detailed knowledge of splenic anatomy, a critical consideration of the intraoperative factors that may lead to splenectomy, and the adoption of a surgical tactic borrowed from the techniques of liver transplant significantly lower the incidence of iatrogenic splenectomy.
Liposome-Mediated Gene Therapy Using HSV-TK/Ganciclovir under the Control of Human PSA Promoter in Prostate Cancer Cells
Authors: Suzuki Satoshi , Tadakuma Takushi , Kunitomi Michito , Takayama Eiji , Sato Masaki , Asano Tomohiko , Nakamura Hiroshi , Hayakawa Masamichi
Published: April 2003

To more accurately determine the tissue-specific expression of the target gene in prostate cancer cells, we introduced the enhancer element (–4,777 to –3,934; PSAR) and the promoter region (PSAP) of the prostate-specific antigen (PSA) gene. Furthermore, to elucidate the advantages of using liposomes as a gene carrier, we screened more than 20 liposome preparations in this study. The 5′ upstream region of PSA gene (PSARPSAP) was conjugated to either the chloramphenicol acetyltransferase (CAT) gene or herpes simplex virus thymidine kinase (TK) gene, and the transfection of these plasmids was carried out using cationic liposomes, DMRIE-C (Gibco) or LipoTAXI (Stratagene). The expression of CAT activity was clearly observed when PSARPSAP-CAT plasmid was transfected into PSA-positive LNCaP cells, whereas no CAT activity was detected in PSA-negative DU145 cells or bladder carcinoma T24 cells. The CAT activity increased after the addition of testosterone. We then evaluated the therapeutic effect of the PSARPSAP-TK plasmid in vitro. When PSARPSAP-TK plasmid was transfected and ganciclovir was added to the medium, the growth of LNCaP cells was inhibited, while no growth inhibition was observed in DU145 cells. Furthermore, this inhibitory effect was observable even when the cells were cultured in a medium supplemented with dialyzed fetal bovine serum. These results suggest that the liposome-mediated transfection of PSARPSAP-TK appears to be a potentially effective approach for selecting the optimal treatment for tumor cells producing PSA even with the low androgen levels seen in patients treated by anti-androgen therapy.
Significance of Fluorescence Cystoscopy for Diagnosis of Superficial Bladder Cancer after Intravesical Instillation of Delta Aminolevulinic Acid
Authors: Ehsan Amgad , Sommer Frank , Haupt Gerald , Engelmann Udo
Published: April 2003

Objectives: Most lesions of superficial bladder cancer may be easily missed during conventional white light cystoscopy. The aim of this work was to evaluate the efficiency of endoscopic fluorescence diagnosis of superficial malignant bladder tumours following intravesical instillation of δ-aminoleviulenic acid. Patients and Methods: 30 patients of suspected or previously diagnosed bladder cancer were subject of evaluation. All patients received 50 ml of a 3% δ-ALA solution intravesically, 2–3 h prior to diagnostic cystoscopy. Fluorescence excitation intraoperatively was achieved by a violet-blue light from a xenon light source. Results: A clear strong red fluorescence colour was observed emitting from all malignant vesical lesions. A diagnostic sensitivity of 98% and specificity of 65% has been determined for this novel diagnostic modality. Conclusion: Fluorescence cystoscopy using δ-ALA is a reliable procedure that can be offered to all patients with suspected bladder cancer lesions.
Differentiation, Ramification and Distribution of Microglia within the Central Nervous System Examined
Authors: Rezaie Payam , Male David
Published: April 2003

The central nervous system contains several populations of mononuclear phagocytes. Principal amongst these are the tissue-resident microglia. These cells are considered to derive from circulating blood progenitors that colonise the developing human nervous system in the second trimester of fetal life. They first appear as amoeboid forms and gradually differentiate to process-bearing ‘ramified’ forms with maturation. Signals driving this transformation are known to be partly derived from astrocytes in vitro, and amoeboid microglial cells progressively ramify when co-cultured with astrocytes, mirroring the ‘differentiation’ of microglia in situ during development. In the adult, microglia occupy distinct non-overlapping territories in their ramified conformations, and are capable of ‘dedifferentiating’ to their activated amoeboid morphological states in a number of pathological circumstances. This is in keeping with the capacity of these cells for a rapid response to inflammatory cues in the CNS. The interchangeable morphological continuum of these cells supports the view that microglia represent a single heterogeneous population of resident mononuclear phagocytes capable of marked plasticity. This review will discuss signals that drive the colonisation, differentiation and ramification of microglia, and examines hypothetical models for their spatial distribution in the adult nervous system.
Nitric Oxide, Peroxynitrite and cGMP in Atherosclerosis-Induced Hypertension in Rabbits: Beneficial Effects of Cicletanine
Authors: Szilvássy Zoltán , Csont Tamás , Páli Tibor , Droy-Lefaix Marie-Thérèse , Ferdinandy Péter
Published: April 2003

We studied the effect of the furopyridine derivative antihypertensive drug, cicletanine, on blood pressure, vascular nitric oxide (NO) and cyclic guanosine 3′:5′-monophosphate (cGMP) content in the aorta and the renal and carotid arteries, aortic superoxide production, and serum nitrotyrosine level in hypertensive/atherosclerotic rabbits. The effect of cicletanine was compared to that of furosemide. Rabbits were fed a normal or a cholesterol-enriched (1.5%) diet over 8 weeks. On the 8th week, the rabbits were treated per os with 2 × 50 mg/kg daily doses of cicletanine, furosemide, or vehicle for 5 days (n = 5–6 in each groups). The cholesterol diet increased mean arterial blood pressure (MABP) from 86 ± 1 to 94 ± 2 mm Hg (p < 0.05). Cicletanine decreased MABP in atherosclerotic rabbits to 85 ± 1 mm Hg (p < 0.05), but it did not affect MABP in normal animals. Furosemide was without effect in both groups. In normal animals, NO content (assessed by electron spin resonance after in vivo spin trapping) in the aorta and the renal and carotid arteries was increased by cicletanine, and the drug increased cGMP in the renal artery as measured by radioimmunoassay. The cholesterol-enriched diet decreased both vascular NO and cGMP and increased aortic superoxide production assessed by lucigenin-enhanced chemiluminescence and serum nitrotyrosine determined by ELISA. In atherosclerotic animals, cicletanine increased NO and cGMP content in the aorta and the renal and carotid arteries and decreased aortic superoxide production and serum nitrotyrosine. Furosemide did not influence these parameters. We conclude that cicletanine lowers blood pressure in hypertensive/atherosclerotic rabbits. The antihypertensive effect of the drug in atherosclerosis may be based on its beneficial effects on the vascular NO-cGMP system and on the formation of reactive oxygen species.
Relationship between Platelets and Neutrophil Adhesion and Neointimal Growth after Repeated Arterial Wall Injury Induced by Angioplasty in Pigs
Authors: Bienvenu Jean-Guy , Tanguay Jean-François , Chauvet Patrick , Merhi Yahye
Published: April 2003

Platelet and neutrophil interactions with injured vascular wall may contribute to restenosis. Their importance was mainly examined following balloon injury of intact arteries. However, dilation of diseased arteries is clinically more relevant and may elicit different responses. We investigated the relationship between platelets and neutrophil adhesion, neointima formation and P-selectin expression on damaged arteries after repeated balloon injury. In an acute single-injury model, 8 pigs were subjected to bilateral carotid angioplasty and sacrificed 1 h later. In a chronic model, 19 pigs were subjected to similar procedures and allowed to recover for 4 weeks; then 18 arteries were redilated at the same previously injured sites (double injury) while the remaining arteries were not redilated and used to investigate the extent and the adhesive properties of the neointima. After single injury, 51Cr-platelet adhesion (×106/cm2) increased significantly from 3.8 ± 0.6 to 45.9 ± 6.5 (p < 0.05) on mildly and deeply injured segments, respectively, and were statistically similar after double injury. After single injury, 111In-neutrophil adhesion (×103/cm2) increased from 226.6 ± 45.5 to 512.5 ± 70.3 (p < 0.05) on mildly and deeply injured segments, and were significantly higher (p < 0.05) after double injury (mild: 1,289.1 ± 227.9 and deep: 2,411.8 ± 333.9). As well, the neo-endothelium expresses P-selectin at 4 weeks and platelet and neutrophil adhesion was directly related to neointimal growth. These results, which indicate ongoing proinflammatory processes 1 month post-angioplasty, suggest that neutrophils may participate in the progression of restenosis.
Failure of L-Nitroarginine to Inhibit the Activity of Aortic Inducible Nitric Oxide Synthase
Authors: Darblade Benoit , Batkai Sandor , Caussé Elisabeth , Gourdy Pierre , Fouque Marie-José , Rami Jacques , Arnal Jean-François
Published: April 2003

Nitric oxide (NO) is produced by a family of three isoenzymes: the endothelial, inducible and neuronal NO synthases. L-Nitroarginine methyl ester (L-NAME) is the most commonly used inhibitor of NO synthase activity. The goal of the present study was to evaluate to what extent L-nitroarginine (L-NA), the in vivo circulating metabolite of L-NAME, blocks NO production in the rat aorta depending on the NO synthase isoform expressed (and evidenced by Western blotting) and on the presence or absence of the extracellular NO synthase substrate L-arginine (100 µM, i.e. the plasma concentration). Intact [endothelium present (E+)] control aortic rings express mainly endothelial NO synthase. L-NA (30–100 µM) induced a dose-dependent contraction (due to blockade of the relaxant properties of NO) irrespective of the presence or absence of L-arginine. In deendothelialized (E–) control aortic rings, the three isoforms of NO synthase are virtually absent (as demonstrated by Western blotting) and L-NA does not elicit any contractile effect. E– aortic rings from lipopolysaccharide (LPS)-treated rats express mainly inducible NO synthase. In these rings, L-NA induced a dose-dependent (0–100 µM) contraction in the absence of extracellular L-arginine, whereas L-arginine (100 µM) completely abrogated the contractile effect of the NO synthase inhibitor. Chronic L-NAME administration (50 mg/kg/day for 4 weeks) elicited the aortic expression of inducible NO synthase, but to a lesser extent (about 5-fold) than in LPS-treated rat aorta. The average plasma concentration of L-NA was 50 ± 10 µM in these rats. In E– rings from these L-NAME-treated rats, L-NA induced a similar contractile response (but smaller in magnitude) to that observed in LPS-treated rat aorta. Altogether, these data suggest that (1) in the presence of a physiological concentration of extracellular L-arginine, L-NA fails to inhibit inducible NO synthase, and (2) chronic L-NAME administration, at a dose commonly given to block NO production in vivo, leaves the activity of inducible NO synthase unaffected.
Enhanced Gene Transfer to Rabbit Jugular Veins by an Adenovirus Containing a Cyclic RGD Motif in the HI Loop of the Fiber Knob
Authors: Hay Carl M. , de Leon Hector , Jafari Jonathon D. , Jakubczak John L. , Mech Christine A. , Hallenbeck Paul L. , Powell Sharon K. , Liau Gene , Stevenson Susan C.
Published: April 2003

Gene therapy using recombinant adenoviral vectors represents a promising therapeutic tool to prevent vein graft stenosis, the main complication of coronary artery bypass grafting. However, the low transduction efficiency of vascular smooth muscle cells and endothelial cells (EC) is a potential limitation, presumably due to the low levels of functional adenovirus receptor (coxsackie:adenovirus receptor; CAR). Designing vectors specifically targeted to αv integrins is a strategy that might overcome the poor expression of CAR in vascular smooth muscle cells and EC. RGD, a receptor-binding motif that can interact with αv integrins, was inserted into the HI loop and at the C-terminus of the adenoviral fiber protein in two separate adenovirus vectors encoding a β-galactosidase reporter gene. Av1nBgCRGD (C-terminus) and Av1nBgHIRGD (HI loop) were evaluated in EC in culture and in jugular vein organ culture. Transduction of primary rat and rabbit EC with Av1nBgHIRGD was significantly more efficient when compared to Av1nBgCRGD or Av1nBg. Transduction of mouse, rat and rabbit jugular veins in organ culture using Av1nBg showed that adenovirus-mediated gene expression was greatest in rabbit jugular veins compared to rat and mouse veins. Av1nBgHIRGD augmented gene expression approximately four-fold in rabbit jugular veins when compared to Av1nBg. Histochemical analysis showed that numerous EC but few smooth muscle cells were transduced at all vector concentrations. A substantial number of adventitial fibroblasts were transduced only at the highest vector concentrations of Av1nBgHIRGD. These findings demonstrate that integrin-targeted vectors allow for enhanced gene delivery to veins and strengthen the viability of adenoviral-mediated gene transfer of therapeutic transgenes to human veins prior to vein grafting.
Biodegradation of the Copolymeric Polylactide Stent
Authors: Hietala Eeva-Maija , Salminen Ulla-Stina , Ståhls Anders , Välimaa Tero , Maasilta Paula , Törmälä Pertti , Nieminen Markku S. , Harjula Ari L.J.
Published: April 2003

The behavior of biodegradable polylactide as a stent material has not yet been fully established in small vessels such as arteries with a diameter <3 mm. The aim of this study was to investigate the long-term effect of a copolymeric polylactide (PLA96) stent. Appropriately sized spiral PLA96 stents were implanted into the infrarenal aortas of 20 rabbits. Intraoperative systemic heparinization (150 IU/kg), perioperative subcutaneous enoxaheparin sodium (10 mg), ticlopidine (250 mg/day) for 1 month, and acetosalicylic acid (12.5 mg/day) were continuously administered. Animals were euthanized according to a fixed timetable for up to 34 months for histologic and scanning-electron-microscopic assessment. Endothelialization was complete within 1 month. In 2 of the 3 aortas sampled 3 months after implantation, a mild inflammatory reaction was visible, with no sign of granulomatous or foreign-body reaction in the vessel wall. Instead, in 1 sample examined at the same time point, neointimal chondroid metaplasia was detected. After 6 months, inflammatory reaction declined in the vessel wall. Hydrolyzation of the stent was histologically evident at 12 months, with mild foreign-body reaction detectable in 2 of 5 aortas sampled at this time point. The stent disintegrated without fragmentation by 24 months, as it was gradually replaced by fibrosis. The vessel lumen remained patent at all time points. We conclude that the PLA96 stent degraded with minimal tissue response within 24 months. PLA96 may thus be a promising stent core material for small vessels in the future, although further investigation is needed to establish its final biocompatibility.
Inhibition by Eicosapentaenoic Acid of Oxidized-LDL- and Lysophosphatidylcholine-Induced Human Coronary Artery Smooth Muscle Cell Production of Endothelin
Authors: Kohno Masakazu , Ohmori Koji , Wada Yoshihiro , Kondo Isao , Noma Takahisa , Fujita Norihiro , Mizushige Katsufumi , Mandal Anil K.
Published: April 2003

The objectives of the present study were (1) to determine whether oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major phospholipid component of oxidized LDL, stimulate the production of endothelin-1 (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells. Oxidized LDL (10–50 µg/ml) and lyso-PC (10–7 to 10–5 mol/l) stimulated ET-1 production in a concentration-dependent manner. By contrast, the effects of native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10–7 to 10–5 mol/l) and oxidized LDL (10–50 µg/ml) significantly induced particulate protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1 production was significantly inhibited by PKC inhibitor, PKC (19–36). EPA (80–160 µmol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 µmol/l) significantly inhibited lyso-PC (10–5 mol/l)- and oxidized LDL (50 µg/ml)-induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC stimulate ET-1 production by a mechanism involving activation of PKC, and that EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL probably through the modulation of PKC in human coronary artery SMCs. EPA may exert an antiatherosclerotic effect, in part, through these mechanisms.
Insulin Action in the Vasculature: Physiology and Pathophysiology
Authors: Mather Kieren , Anderson Todd J. , Verma Subodh
Published: April 2003

Studies to date have provided convincing evidence that insulin has an important role in the normal functioning of the vasculature from the perspective of the regulated delivery of nutrients to a tissue bed. This is mediated by an effect on the endothelium analogous to other endothelial responses, and insulin resistance is reflected in, and in part due to, impaired vasodilatory actions of insulin. Because insulin normally stimulates the net production of nitric oxide, which is beneficial in both the short term for vasomotion and antithrombosis, and the long term for inhibition of smooth muscle cell growth and migration, vascular insulin resistance also has important implications for vascular pathophysiology. Further, recent evidence suggests that the hyperinsulinemia accompanying insulin resistance may aggravate this situation by augmenting the endothelial production and release of endothelin-1. The investigation of insulin resistance in the vasculature provides not only a unique and physiologically relevant window onto vascular pathology, but also an opportunity for therapeutic targeting in individuals affected by the clinical states of insulin resistance. The present review highlights the importance of insulin sensitivity in the maintenance of endothelial function and explores the relationships between vascular insulin resistance and whole body glucose disposal. In addition, the recent evidence linking insulin to endothelin-1 production is discussed. Improving insulin sensitivity with insulin sensitizers such as rosiglitazone may represent an important advance in our ability to improve vascular dysfunction in diabetes.
Plasmin-Mediated Fibroblast Growth Factor-2 Mobilisation Supports Smooth Muscle Cell Proliferation in Human Saphenous Vein
Authors: George Sarah J. , Johnson Jason L. , Smith Melanie A. , Jackson Christopher L.
Published: April 2003

The focus of this study was identification of the contribution of the plasminogen activator-plasmin system to smooth muscle cell proliferation and migration in human saphenous vein. Segments of human saphenous vein were grown in organ culture for up to 14 days. Smooth muscle cell proliferation and migration were measured by incubating vein segments in bromodeoxyuridine, and smooth muscle cell death was detected by in situ end-labelling. Tissue-type (tPA) and urokinase-type (uPA) plasminogen activator enzymic activities were detectable in cultured saphenous vein segments, and were concentrated in focal zones. Inhibition of plasmin activity with α-N-acetyl-L-lysine methyl ester (NALME) or of uPA activity with a neutralising antibody caused significant decreases in smooth muscle cell proliferation in the media and the intima, but no significant changes in smooth muscle cell migration. Intimal thickness was also significantly decreased. Incubation with plasminogen or plasmin caused fibroblast growth factor-2 (FGF2) to be released into the medium. Addition of FGF2 to segments cultured with NALME reversed the inhibition of smooth muscle cell proliferation, and blocking the activity of FGF2 with a neutralising antibody caused a significant decrease in medial smooth muscle cell proliferation. These data suggest that plasmin mobilises FGF2 bound to the extracellular matrix of human saphenous vein, so that it can support smooth muscle cell proliferation and intimal thickening.
The Frequency of Inherited Disorders Database: Prevalence of Huntington Disease
Authors: Al-Jader Layla N. , Harper Peter S. , Krawczak Michael , Palmer Stephen R.
Published: April 2003

A database of the frequency of human inherited disorders is being established for use in a clinical context, in medical research, for epidemiological studies, and in the planning of genetic services. Each entry includes the disease name categorized by organ system, an Online Mendelian Inheritance in Man (OMIM) number, the mode of inheritance, the population origin, a prevalence and/or incidence rate and a literature reference. The Frequency of Inherited Disorders Database (FIDD) currently contains 1,580 entries relating to 280 different Mendelian disorders. FIDD will be prospectively maintained and can be accessed at http://www.uwcm.ac.uk/uwcm/mg/fidd/. A more refined and systematic literature search that will serve to expand the size, scope and scale of the database is currently in progress. The coverage of neurological and neuromuscular disorders is however considered to be nearly complete. In this first description of FIDD, Huntington disease was used to illustrate the structure and scope of the database as well as its potential scientific utility. A total of 100 published articles on the prevalence of Huntington disease were appraised. Prevalence and incidence rates varied between different ethnic groups and between different countries. Possible reasons for this variation are discussed.
Pathophysiologic Mechanisms in the Development of Age-Related White Matter Changes of the Brain
Authors: Fazekas Franz , Schmidt Reinhold , Scheltens Philip
Published: April 2003

Magnetic resonance imaging (MRI) has dramatically enhanced our capability of detecting age-related changes of the brain even before they become clinically apparent. Among those are preferentially alterations of the white matter in periventricular, deep and subcortical locations which display high signal intensity on both proton density- and T2-weighted images. Correlative histopathologic findings show hyperintense periventricular capping of the frontal horns to reflect predominantly a specific anatomic situation characterized by loosely arranged fine-fiber tracts with low myelin and high extracellular fluid content. A smooth halo of periventricular hyperintensity has been linked to disruption of the ependymal lining with subependymal gliosis and concomitant loss of myelin. In contrast, punctate, early confluent and confluent hyperintensities in the deep and subcortical white matter as well as irregular periventricular hyperintensity appear to be of vascular origin. Punctate lesions tend to correspond to a perivascular reduction in myelin content with atrophy of the neuropil and seem to constitute a negligeable extent of tissue damage from low permeability through thickened arteriolar walls. Early confluent and confluent hyperintensities, however, indicate more extensive ischemic damage consistent with advanced microangiopathy.
Neuronal Substrates for Semantic Memory: A Positron Emission Tomography Study in Alzheimer’s Disease
Authors: Hirono Nobutsugu , Mori Etsuro , Ishii Kazunari , Imamura Toru , Tanimukai Satoshi , Kazui Hiroaki , Hashimoto Mamoru , Takatsuki Yoko , Kitagaki Hajime , Sasaki Masahiro
Published: April 2003

We examined 57 patients with mild Alzheimer’s disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by 18F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.
Senile Dementia of the Neurofibrillary Tangle Type: A Comparison with Alzheimer’s Disease
Authors: Yamada Masahito , Itoh Yoshinori , Sodeyama Nobuyuki , Suematsu Naomi , Otomo Eiichi , Matsushita Masaaki , Mizusawa Hidehiro
Published: April 2003

A subset of senile dementia, ‘senile dementia (SD) of the neurofibrillary tangle (NFT) type’ (SD-NFT), is characterized by numerous NFTs in the hippocampal region and absence or scarcity of senile plaques throughout the brain. To elucidate the pathogenesis of SD-NFT in comparison with Alzheimer’s disease (AD), we investigated the hippocampal lesions and analyzed the tau gene. The hippocampal regions from 5 patients with SD-NFT were neuropathologically evaluated in comparison with AD and nondemented control subjects. The tau gene was analyzed in 3 patients with SD-NFT. The densities of NFTs in the CA1/subiculum and entorhinal cortex of SD-NFT were significantly higher than those in AD. However, hippocampal atrophy, neuronal and synaptic loss, and astrocytic and microglial proliferation in SD-NFT were significantly mild compared with AD. There was no significant difference between SD-NFT and AD in the immunoreactivities of NFTs with different anti-tau antibodies. No mutation was found in the tau gene from the SD-NFT patients. Our results indicate that the neurodegenerative process with NFT formation of the hippocampal region in SD-NFT would be different from that in AD.
Mild Amyloid Pathology in the Primary Visual System of Nonagenarians and Centenarians
Authors: Leuba G. , Saini K. , Zimmermann V. , Giannakopoulos P. , Bouras C.
Published: April 2003

In order to study the patterns of Alzheimer disease (AD)-related pathology in the primary visual system of the oldest old, we performed a quantitative analysis of senile plaques (SP), diffuse β amyloid (Aβ) deposit and neurofibrillary tangle (NFT) distribution in primary area 17, and a semi-quantitative analysis in the dorsal lateral geniculate nucleus (LGN), lateral inferior pulvinar (LIP) and superior colliculus (SC) of 21 individuals aged between 93 and 102 years. Among them, 10 cases were considered as non-demented (ND), while 9 presented very mild cognitive impairment (VMCI), and 2 cases had a clinical diagnosis of AD. Silver methenamine and Gallyas staining, Aβ and tau immunostaining revealed the distribution of AD lesions. In primary area 17, most cases, either ND or with VMCI displayed a low to medium number of SP. There was no significant difference in SP and Aβ deposit densities between ND and VMCI groups. On the whole, 0.4–2.4% of the cross-sectional cortical area was covered with Aβ deposits. Only 6 cases, either ND or with VMCI, were totally devoid of SP and diffuse Aβ deposits. Among the subcortical structures, the LIP and SC exhibited low densities of SP and Aβ deposits in about half of the ND and VMCI cases, while the LGN was totally spared. NFT were almost absent in area 17 and subcortical nuclei of ND and VMCI cases. These data imply that the ageing of the primary visual system in ND and VMCI nonagenarians and centenarians is characterised by the frequent development of mild amyloid pathology in area 17 in the absence of NFT. In agreement with previous studies in very old cohorts, they also suggest that amyloid deposition is not related to the early stages of the dementia process in the oldest old.
Evaluation of the Quality of Life in Dementia with a Generic Quality of Life Questionnaire: The Duke Health Profile
Authors: Novella J.L. , Ankri J. , Morrone I. , Guillemin F. , Jolly D. , Jochum C. , Ploton L. , Blanchard F.
Published: April 2003

Objective: The study was designed to determine the acceptability, feasibility and validity of measuring quality of life in a representative sample of dementia patients with a generic instrument, the Duke Health Profile. Method: The French version of the Duke Health Profile was administered to 148 subjects with a mental disorder according to the DSM-III-R diagnostic criteria. The feasibility and acceptability of employing the instrument were determined by the refusal rate, the type of administration, and the percentage and distribution of missing data. Reliability was determined with Cronbach’s α coefficient. Instrument reproducibility was assessed with the intraclass correlation coefficient for test-retest values. Internal construct validity was determined by factor analysis. Discriminant capacity was determined by comparing the average scores on each measure among patients with and without an additional chronic pathology. The measurements obtained were compared by source of information (patient, family proxy and care provider proxy). Results: The feasibility and acceptability of the instrument was good. Only 2% of the patients refused to complete the questionnaire. Help from the interviewer was necessary in 79% of the cases. The average completion time was 10.6 min. Missing data exist in only 3.5% of the cases on average, except among patients with severe dementia (Mini Mental State Examination <10). For reliability, internal consistency was acceptable (Cronbach’s coefficient α = 0.5–0.7) when the self-esteem (0.23) and social health (0.26) concepts were eliminated. Reproducibility as measured by test-retest scores was moderate to good (intraclass correlation coefficient r = 0.53–0.80), except for anxiety (0.48) and perceived health (0.45). Severity of dementia mainly affected the feasibility, acceptability and reproducibility of the instrument. The family proxy seemed to agree more with the patient than did the care provider proxy. Conclusion: Quality of life can be measured in patients with dementia, but special tools need to be developed for severe dementia.
Homocysteine and Cognitive Decline in Healthy Elderly
Authors: McCaddon Andrew , Hudson Peter , Davies Gareth , Hughes Alan , Williams John H.H. , Wilkinson Clare
Published: April 2003

Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer’s disease (AD), vascular dementia and ‘age-associated memory impairment’. Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period. Homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance independently of age, sex, education, renal function, vitamin B status, smoking and hypertension (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills.