bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates of Cognitive Decline in Alzheimer’s Disease and Dementia with Lewy Bodies
Authors: Helmes Edward , Bowler John V. , Merskey Harold , Munoz David G. , Hachinski Vladimir C.I.
Published: April 2003

Increased interest in types of dementia has developed as more cases are identified in aging populations. Here we compare the rates of cognitive decline over time in three groups with dementia from the University of Western Ontario Dementia Study: Alzheimer’s disease (AD), dementia with Lewy bodies and a group with both AD and Lewy bodies. All diagnoses were verified by autopsy using standard diagnostic methods. Cognitive impairment was measured with the Extended Scale for Dementia (ESD). Members of each group with dementia were age and sex matched with individuals without dementia as controls. The 15 cases of AD, 7 cases with Lewy bodies and 8 cases with both conditions were all free of significant vascular disease. Linear regression was used to determine the rate of changes in ESD scores over time in months. All three control groups showed no change in cognitive status over time. As expected, all groups with dementia showed progressive cognitive impairment. Analysis of the slope parameter showed that all groups deteriorated at the same rate of approximately 2 ESD points per month. Quadratic models fit better than simple linear models in all groups. Results suggest that the final rate of cognitive decline in dementia may not necessarily reflect the underlying cause.
Preliminary Exploration of the Clinical Effect of Bleomycin on Craniopharyngiomas
Authors: Jiang Rongcai , Liu Zonghui , Zhu Cheng
Published: April 2003

Objective: To investigate the antitumor effect of bleomycin on craniopharyngiomas. Methods: A series of cystic craniopharyngiomas were randomly divided into three groups: (A) intracystic chemotherapy with bleomycin; (B) intracystic chemo-radiotherapy with bleomycin and 32P; (C) intracystic radiotherapy with 32P and 0.9% saline. The agents were injected into the cysts through stereotactically inserted silicone tubes. Follow-up was done for a minimum of 6 months. Outcome was based on a comparison of the volume of cysts before treatment and at follow-up. The index and lactate dehydrogenase (LD) of the cystic fluids, blood and cerebrospinal fluids and the endocrine function of these patients were determined before and after therapy. Results: 19 patients finished the whole therapeutic course: 5 from group A, 9 from group B and 5 from group C. Four tumors in group A were polycystic, and the drug was selectively injected into the largest cyst. At follow-up, the volumes of the cysts in groups A and B regressed from 92 to 0%, while the drug-free cysts enlarged. In group B, 6 cysts almost disappeared and another 3 regressed from 78 to 57%. In group C, one cyst progressed and the others shrank by different degrees, but none disappeared completely or nearly. All patients in groups A and B had fever of different degrees, which resolved spontaneously in 8–24 h. The complications in group B included hyponatremia in 1 patient, and both adephagia obesity and cerebral infarction in 2 patients (1 of whom died after 6 months). Apart from the oculomotor paralysis occurring in 1 patient, the remainder of group C had no other severe complications. Blood chemistry, liver, kidney, pituitary and endocrinal functions changed little during the course in all these 19 patients. LD and its isoenzymes from the cystic fluids, CSF and serum showed no marked change after bleomycin injection. Conclusion: Bleomycin injected into cysts of craniopharyngiomas causes the tumor to shrink. When 32P is added, the therapeutic effect seems better than treatment with either 32P or bleomycin alone. Blood chemistry, liver, kidney and endocrine functions change little irrespective of the therapy applied. However, the combination of chemotherapy and radiotherapy may severely disturb both serum electrolytes and endocrine function. LD and its isoenzymes in the cystic fluids, CSF and serum may not change after bleomycin treatment.
Brain Metastasis: Experience of the Xi-Jing Hospital
Authors: Wang Li Gen , Guo Yan , Zhang Xiang , Song Shao Jun , Xia Jie Lai , Fan Feng Yun , Shi Mei , Wei Li Chun
Published: April 2003

Background: The management of metastatic brain tumors is an important issue in patients with malignant tumors or cancer. The authors summarize the results of patients with brain metastases treated at the Xi-Jing Hospital during a 10-year period, in order to assess the best modality of treatment for patients with brain metastases. Methods: Between 1990 and 2000, 463 patients with brain-metastatic tumors were treated at the Xi-Jing Hospital of the Fourth Military Medical University, Xian, China. In most patients, the pathologic diagnosis of primary cancer was obtained before they were referred for their brain metastasis. There were 34 (8.42%) cases with an unknown primary cancer site at the time of initial presentation. Patients were grouped according to treatment methods, which included neurosurgical craniotomy (NS; 130 patients), whole-brain radiotherapy (WBRT; 120 patients). Linac XKnife radiosurgery (RS; 130 patients) and Linac XKnife radiosurgery plus WBRT (RT; 83 cases). Survival was measured from the time of treatment and was analyzed by the Kaplan-Meier product-limit method and then plotted. Differences between curves were evaluated using the log-rank test. Multivariate factors associated with survival were analyzed using the Cox proportional hazards model. Results: The survival time was 68.4 ± 7.20 weeks after NS, 51.3 ± 5.04 weeks after WBRT, 67.9 ± 3.68 weeks after RS and 89.7 ± 4.50 weeks after RT. The presence of active systemic cancer in a larger number of metastatic tumors was associated with a poor survival (p = 0.0003 and 0.0000). The female patients showed better survival rates over the male ones (p = 0.0000). Patients treated with RT had a better survival than those treated with NS, WBRT and RS (p = 0.0048, 0.0000 and 0.1222, respectively), although the latter did not show statistical significance. Conclusions: RS was an effective modality for patients with brain metastases, and if combined with WBRT, survival was better. Progression of systemic cancer and the number of metastatic tumors were the most significant factors for a poor survival after treatment of the brain metastases.
Extraventricular Intracisternal Obstructive Hydrocephalus – A Hypothesis to Explain Successful 3rd Ventriculostomy in Communicating Hydrocephalus
Authors: Kehler U. , Gliemroth J.
Published: April 2003

The basis of successful 3rd ventriculostomy in cases of communicating hydrocephalus is not yet understood. We performed 3rd ventriculostomies in 5 patients with free cerebrospinal fluid (CSF) communication from the ventricles to the cisterna magna. Preoperative magnetic resonance images (MRIs) showed dilated ventricles, a downward bulging floor of the 3rd ventricle (interpreted as a sign of pressure gradient between the ventricles and basal cisterns) and a free communication to an enlarged cisterna magna. The other basal cisterns were of normal or smaller size. All patients recovered from their clinical symptoms and none of them needed a shunt. The hypothesis of an intracisternal CSF pathway obstruction (e.g. between the cisterna magna and the prepontine cistern) could explain the MRI findings, although such an obstruction cannot be directly visualized. It would also explain the successful 3rd ventriculostomies in these cases.
Congenital Thoracic Cord Segmental Amyelia: A Rare Manifestation of Segmental Spinal Dysgenesis
Authors: Desai Ketan , Nadkarni Trimurti , Bhayani Rajendra , Goel Atul
Published: April 2003

Segmental spinal dysgenesis (SSD) is a rare congenital abnormality in which a segment of the spine and spinal cord fails to develop properly. We report a case of a 4-year-old female child who was born prematurely with a permanent neurological deficit in the lower limbs and sphincter incontinence. Radiological investigations revealed segmental agenesis of the thoracic spinal cord (D8–D11 vertebral levels) with an associated vertebral bony anomaly. The pathogenesis of this rare form of SSD syndrome is discussed and the relevant literature is briefly reviewed.
Prenatal Diagnosis of a Large Centromeric Heteromorphism of Chromosome 12: Implications for Genetic Counseling
Authors: Chantot-Bastaraud Sandra , Siffroi Jean Pierre , Berkane Nadia , Heim Nazbanou , Herve François , Uzan Serge , Vendrely Eric
Published: April 2003

Chromosomal centromeric variants can be found in the course of a prenatal diagnosis. When following the discovery of fetal abnormalities at ultrasound examination, such variants may lead to some difficulties in genetic counseling. Here we describe a new heteromorphism implicating chromosome 12, found in a fetus with a suspicion of microcephaly, and we discuss its prognostic value.
Role of Commensal Bacteria in Chronic Experimental Colitis: Lessons from the HLA-B27 Transgenic Rat
Authors: Rath Heiko C.
Published: April 2003

Rats on Lewis or Fischer background, transgenic for human HLA-B27 and β2-microglobulin genes spontaneously develop colitis, gastritis, arthritis, dermatitis, orchitis, epididymitis, carditis, alopecia and nail changes. Disease susceptibility correlates with the gene copy number and is influenced by the genetic background. The pathomechanism in this model is still not completely understood. Cell transfer experiments indicate an essential role of HLA-B27 expression in bone marrow-derived cells. On Fischer background the onset of colitis occurs at 2 months of age, peaks at 3 months of age, and plateaus. Histologic findings include inflammatory cell infiltration, mostly limited to the mucosa, crypt hyperplasia, reduction of goblet cells, occasionally crypt abscesses and early ulcers. There is evidence that normal luminal bacteria play an essential role in initiating and perpetuating chronic colitis and gastritis in HLA-B27 transgenic rats: Transgenic rats raised under germ-free conditions do not develop gastrointestinal disease, whereas transgenic littermates exposed to specific pathogen-free bacteria develop colitis and gastritis within 2–4 weeks. Obligate anaerobic bacteria, especially Bacteroides spp., may play a predominant role since metronidazole prevents colitis and transgenic germ-free rats contaminated with a cocktail of six obligate and facultative anaerobic bacteria develop colitis and gastritis only in the presence of Bacteroides vulgatus. Luminal bacteria may also be involved in trafficking and homing of inflammatory cells into remote organs, since varying cecal bacterial composition does not only alter local inflammation but also influences gastritis. Lymphocyte transfer experiments indicate a specific response to luminal bacteria. In summary, this animal model is suitable for investigating the influence of normal luminal bacteria on the cellular immune mechanism in chronic intestinal inflammation.
Role of Gamma Delta T Cells in Inflammatory Bowel Disease
Authors: Kühl Anja A. , Loddenkemper Christoph , Westermann Jürgen , Hoffmann Jörg C.
Published: April 2003

γδ T cells have previously been shown to play a protective role in various animal models of chronic inflammation (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis, and non-obese diabetes). This immunoregulatory potential is exerted by synthesizing various anti-inflammatory cytokines and growth factors (e.g., transforming growth factor-β). As the normal balance between inflammatory and regulatory cytokines is perturbed in inflammatory bowel disease (IBD) a protective effect of γδ T cells seems likely. This notion is supported by our finding of increased mortality of rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis following γδ T cell depletion. In contrast, no effect was observed after depletion of γδ T cells in a Crohn’s disease animal model with terminal ileitis (TNFΔARE mice). Therefore, future studies must further define where in the intestinal immune system γδ T cells exert their protective function and how this can be used in the treatment of IBD.
Functional Involvement of CD44 Variant 7 in Gut Immune Response
Authors: Wittig Bianca M. , Stallmach Andreas , Zeitz Martin , Günthert Ursula
Published: April 2003

A major problem in inflammatory bowel disease (IBD) is the accumulation of highly activated T-helper cells that are refractory to apoptosis induction. Hence, persistent inflammatory lesions are prevalent and are the basis of chronic disease. In IBD upregulation of costimulatory molecules on lamina propria lymphocytes has been described leading to apoptosis resistance. CD44 is a cell adhesion molecule and a signalling receptor that functions as a costimulatory molecule in T-cell activation. Several variant isoforms of CD44 (CD44v) are expressed by alternative splicing of variant exons encoding extracellular regions. Particularly isoforms containing CD44v7 are expressed on T cells and macrophages in T-helper-1 (Th1)-mediated chronic inflammation and autoimmune diseases. In this review recent data on the functional involvement of CD44v7 isoforms in IBD are discussed. In a mouse model of experimental colitis blockade or deletion of CD44v7 protects mice from severe intestinal inflammation by inducing apoptosis in lamina propria mononuclear cells. Recently, we observed that in lamina propria mononuclear cells from the inflamed but not uninflamed mucosa of patients with Crohn’s disease, blockade of CD44v7 isoforms also induces apoptosis. The finding that obstruction of CD44v7 isoforms can antagonize Th1-cytokine-dependent immune pathology identifies CD44v7 as a target in the treatment of inflammatory diseases such as IBD, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases in which CD44v7 isoforms are upregulated.
Nitric Oxide Production and Arachidonic Acid Metabolism in Platelet Membranes of Coronary Heart Disease Patients with and without Diabetes
Authors: Tretjakovs Peteris , Kalnins Uldis , Dabina Inese , Erglis Andrejs , Dinne Iveta , Jurka Antra , Latkovskis Gustavs , Zvaigzne Agnis , Pirags Valdis
Published: April 2003

Aim: To evaluate the levels of nitrite (NO–2) and nitrate (NO–3) ions and the incorporation of [3H]arachidonic acid (AA) into phospholipids of platelet membranes from coronary artery disease (CAD) patients with and without diabetes (NIDDM). Subjects and Methods: Eighteen CAD patients (group A), 18 CAD patients with NIDDM (group B), and 20 healthy controls (group C) without dyslipidemia, peripheral vascular disease and hypertension were included in the study. The groups were matched for age, sex and body mass index. The diagnosis of CAD was confirmed by coronary angiography. The nitric oxide end products (NOx), NO–2 plus NO–3 ions in platelet membranes, were determined using a spectrophotometric method based on the Griess reaction. The turnover of phospholipids was evaluated by incorporation of [3H]AA into platelet membrane phospholipids. Results: A significantly smaller amount of NOx ions was in the platelet membrane of groups A (40 ± 8 µmol/l) and B (29 ± 10 µmol/l) than C (57 ± 6 µmol/l), p < 0.001. Conversely a significantly greater amount of [3H]AA was incorporated into platelet phospholipids of group B patients (5,123 ± 1,637 dpm/mg) than groups A (3,159 ± 1,253 dpm/mg; p < 0.002) and C (1,621 ± 417 dpm/mg). An inverse correlation between [3H]AA incorporation and NOx levels was established: r = –0.76 (p < 0.05, n = 36) in CAD patients. Conclusions: Diabetes in CAD patients decreased the ability to produce platelet-derived NO and affects AA metabolism. This may result in higher platelet sensitivity to aggregating stimuli.
Treatment of Rubeosis iridis with Photodynamic Therapy with Verteporfin – A New Therapeutic and Prophylactic Option for Patients with the Risk of Neovascular Glaucoma?
Authors: Müller Valeska A. , Ruokonen Peter , Schellenbeck Meike , Hartmann Christian , Tetz Manfred
Published: April 2003

Patients with ischaemic retinopathy who show iris neovascularization despite panretinal laser photocoagulation (PRP) very often develop a neovascular glaucoma. Photodynamic therapy (PDT) has been shown to occlude neovascularization without damage to physiologic vessels or adjacent tissue in the treatment of choroidal neovascularization (CNV) and might also be of value for patients with neovascular glaucoma who did not benefit from the PRP. First results of a monocentre, open label, intra-individual controlled, pilot phase I/II, dose-finding study demonstrate that PDT with verteporfin is capable of occluding neovascular vessels for a defined period of time without damaging adjacent tissue or physiologic iris vessels. Whether this vessel occlusion will have an impact on the progression of rubeosis or neovascular glaucoma will be the subject of further investigation.
Glare Disability and Driving Safety
Authors: Babizhayev Mark A.
Published: April 2003

Purpose: Increasing investigation of the visual elements of safe driving environments may be of great benefit to society. Visual disability appears to be only one of many visual factors related to traffic accidents. The purpose of this article was to examine the type of visual impairment mediated by the increased glare sensitivity in adult drivers using the original halometer glare test. Methods: In this article, the visual sensory, cognitive and motor functions relevant to driving, their measurement, the epidemiology and prevention of age-associated functional impairments and the relationship of functional impairments to both self-reported driving and the imposition of legal restrictions are reviewed. Results: The problem of night and tunnel driving is the most urgent in relation to the effects of glare from vehicle headlights on motion perception of drivers. The reduced mesopic vision and increased sensitivity to glare are accompanied by an increased risk of nighttime accidents. Elderly drivers and patients with beginning cataract cannot sufficiently fulfill the criteria for night driving ability because of contrast and glare sensitivity. It is indispensable for the parameters mentioned to be carefully measured and for drivers to be informed that night driving ability may be impaired, even if visual acuity is sufficient. Conclusions: It would be advisable for traffic safety if simple tests for contrast and glare sensitivity were implemented for vehicles and/or were regularly added to the requirements for a driver’s licence, at least for older drivers. The age, functional status and test result limits should be defined to avoid a risk factor in traffic.
Effect of a Yellow Filter on Mesopic Contrast Perception and Differential Light Sensitivity in the Visual Field
Authors: Pérez María Jesús , Puell María Cinta , Sánchez Celia , Langa Antonio
Published: April 2003

Purpose: Previous studies on the effects of yellow filters in the visual performance have been carried out, presenting discrepancies among the different investigations. Our study reports the influence of the yellow filter without residual reflections on contrast perception and differential light sensitivity (DLS) under mesopic conditions. Methods: Contrast sensitivity, low contrast visual acuity and luminance thresholds in the central visual field (30°) were measured in a group of 38 adult subjects with and without a coated yellow lens (482-nm cut-off) under mesopic conditions. Results: The contrast sensitivity mean was significantly better with the filter at low- and middle-range spatial frequencies (1.5 cycles/degree p = 0.002 and 6 cycles/degree p = 0.02). At 5% contrast, the mesopic low contrast visual acuity improved significantly (p = 0.004) when interposing the yellow filter. The increase in DLS was statistically significant [e.g. all visual fields p = 0.0003 and macular visual field (9.5°) p = 0.00001] through the yellow filter on the different established areas of the visual field (30°). Conclusions: The yellow filter without residual reflections had a positive influence on the brightness and contrast perception of healthy subjects, for which its use would be beneficial under mesopic conditions.
Stroke Units and Stroke Services in Portugal
Authors: Melo Teresa P. , Ferro José M.
Published: April 2003

Stroke is the first cause of death in Portugal. In 1999 more than 70,000 patients with a stroke were admitted to public hospitals, with total hospitalisation costs of EUR 188 million. Stroke patients are traditionally treated in the departments of medicine and/or neurology. In 2001 the Department of Health approved a rapid transport system of acute stroke victims to the stroke units as well as ‘Stroke Unit Guidelines’. The aim of these guidelines is to define norms facilitating the launch of stroke units in all Portuguese hospitals admitting more than 300 stroke patients a year. By July 2002, five stroke units were already operating.
The Polish Experience in Early Stroke Care
Authors: Członkowska Anna , Milewska Danuta , Ryglewicz Danuta
Published: April 2003

Stroke units are being organised in Poland since 1997. To ensure easy access to stroke care, 120 specialised units need to be created. There were 23 stroke units in Poland in the year 2000. Only 12 of them fulfilled the criteria of a standard stroke unit. Significant differences in stroke fatality were noted between well- and as yet insufficiently organised units. These results indicate a need for monitoring the implementation of the basic standards in stroke units.
Stroke Units and Stroke Services in Germany
Authors: Busse Otto
Published: April 2003

Background/Objectives: The German stroke units are sub-intensive units with the possibility of continuous monitoring of vital parameters. This is the main difference to Scandinavian and British non-intensive combined acute and rehabilitation stroke units. Germany has 56 regional and 50 local stroke units, and standards differ between them. Nearly 30% of all strokes in Germany are treated in these units. The German stroke units are cost intensive and unfortunately their effectiveness has not been proven yet.
An in vitro Comparison of a Combined FOTI/Visual Examination of Occlusal Caries with Other Caries Diagnostic Methods and the Effect of Stain on Their Diagnostic Performance
Authors: Côrtes D.F. , Ellwood R.P. , Ekstrand K.R.
Published: April 2003

The aims of this in vitro study were to compare the combination of FOTI and visual inspection to other diagnostic methods for the detection and evaluation of the depth of occlusal caries and assess the effect of stain on diagnostic performance. Five diagnostic methods (combined FOTI/Visual (CFV), Visual, FOTI, DIAGNOdent and Electrical Caries Monitor) were considered. Histological validation was performed in the 152 occlusal molar sites (111 teeth) using 350-µm sections and a stereomicroscope. The rank correlation coefficients with histology ranged from 0.42 (DIAGNOdent) to 0.66 (CFV). The area under the ROC curves (AUC) for enamel lesions ranged from 0.82 (ECM) to 0.88 (CFV) and from 0.81 (DIAGNOdent) to 0.91 (CFV) for dentine lesions. The AUC at the dentine level for CFV and FOTI were similar (p > 0.05), but the AUC for CFV was significantly greater than for visual (p < 0.001), DIAGNOdent (p = 0.005) and the ECM (p = 0.04). FOTI was found to be particularly useful for the detection of dentine lesions. The exclusion of stain and brown spot lesions improved performance for all methods. It is concluded that CFV is useful for the determination of occlusal lesion depth and that in the presence of stain and brown spot lesions different cut-off points may be required for the ECM and DIAGNOdent to identify dentine lesions.
Holographic Interferometry of Excimer-Laser-Ablated Bovine Eyes: First Results
Authors: Förster Werner , Stupp Tobias , Kasprzak Henryk
Published: April 2003

Purpose: To investigate the effects of areal corneal ablations of different depth on the biomechanical properties of the cornea. Method: The qualitative change of the holographic interferometric fringe pattern of enucleated bovine corneas due to areal mechanical ablations (group A) of 35% and 70% depth of the central cornea and 15, 30, and 50% excimer laser ablations in each eye (group B) was investigated. Results: Ablations of 50% (group B) and 70% (group A) showed a significant variation of the fringe pattern as an effect of the corneal weakening. 15% excimer laser ablations of 5 mm diameter did not result in noticeable changes of the fringe pattern. Half of the 30% ablated corneas in group B showed newly appearing fringes within the area of ablation, indicating a local reduction of the corneal stiffness after ablation. Conclusion: The thickness of the remaining tissue is very important for the biomechanical behavior of the cornea after areal ablations. There are interindividual differences regarding the change of material properties due to excimer laser ablation of 30% depth of ablation.
Ocular Perfusion Pressure and Visual Field Indice Modifications Induced by α-Agonist Compound (Clonidine 0.125%, Apraclonidine 1.0% and Brimonidine 0.2%) Topical Administration
Authors: Costagliola Ciro , Parmeggiani Francesco , Ciancaglini Marco , D’Oronzo Emanuele , Mastropasqua Leonardo , Sebastiani Adolfo
Published: April 2003

Objective: The aim of this study was to verify the acute effects of α-adrenoreceptor agonist eyedrop administration on visual field parameters and ocular perfusion pressure (OPP) in patients affected by primary open-angle glaucoma. Methods: A prospective, randomized double-blind study was carried out. Sixty-four glaucomatous subjects were enrolled in the clinical trial and subsequently separated into four study groups, of 16 patients each, to compare the systemic and ocular effects of placebo, clonidine 0.125%, apraclonidine 1.0% and brimonidine 0.2%. Results: No significant variations in the ocular or systemic parameters were observed after placebo administration. All the α-adrenoreceptor agonist compounds induced a significant reduction of the intraocular pressure. Clonidine induced significant modifications of mean blood pressure, OPP and visual field indices. The acute administration of apraclonidine did not affect both mean blood pressure and OPP, but a worsening of the visual field was nevertheless recorded. The analyzed parameters did not significantly vary after brimonidine instillation. Conclusions: The present findings demonstrate that the lack of effects on the blood flow and the absence of vasomotor activity at the level of the posterior pole exhibited by brimonidine is related to its α-2 selectivity, as appears by comparing this compound with the other α-agonists available for the management of glaucoma.
The Effects of Topical Corticosteroids and a Coal Tar Preparation on Dithranol-Induced Irritation in Patients with Psoriasis
Authors: Swinkels O.Q.J. , Kucharekova M. , Prins M. , Gerritsen M.J.P. , van der Valk P.G.M. , van de Kerkhof P.C.M.
Published: April 2003

Dithranol has been a mainstay in the treatment of psoriasis for more than 80 years. Although a safe approach, the irritation of the clinically uninvolved perilesional skin remains a major limitation of this treatment. Corticosteroids and coal tar solution have an anti-inflammatory potential. The aim of the present study was to investigate the clinical and cell-biological effects of two topical corticosteroids and a coal tar preparation on dithranol-irritated skin. During 4 consecutive days, 2% dithranol cream was applied to six uninvolved skin sites (3 cm in diameter) on the lower back of 9 patients with psoriasis. Dithranol was left on the skin for 1 h, subsequently removed with water and soap and the skin was dried with a towel. Subsequently, Site 1 was treated with 0.05% clobetasol-17-propionate ointment (CP), Site 2 with unguentum cetomacrogolis (vehicle 1), Site 3 with 0.005% fluticasonpropionate ointment (FP), Site 4 with 10% coal tar solution in lanettewax cream (CTS), Site 5 was left untreated (control) and Site 6 was treated with lanettewax cream (vehicle 2). Erythema, oedema and vesicle formation was scored every day. On day 5, punch biopsies were taken from the six sites. The expression of epidermal proliferation, differentiation and inflammation markers and the clinical irritation scores indicate that the application of a high potency corticosteroid (CP) is the best approach to minimise dithranol irritation, whereas CTS had virtually no effect on dithranol irritation during this 4-day experimental model.
Colocalization of Progesterone Receptors and Thyroid Hormone Receptors Alpha in the Ovine Diencephalon: No Effect of Estradiol
Authors: Dufourny Laurence , Skinner Donal C.
Published: April 2003

Progesterone and thyroid hormones are key hormones in the control of reproduction in the ewe since both have been shown to inhibit GnRH secretion. GnRH neurons do not express progesterone receptors (PR) but half of them contain thyroid hormone receptors α (THRα), two nuclear receptors potentially able to act on gene transcription. PR and THRα distributions overlap in most regions of the ovine preoptic area (POA) and hypothalamus. To determine whether progesterone and thyroid hormones may also have common neuronal targets for the control of GnRH cell activity, we searched for coexpression of PR with THRα within neurons of the POA and hypothalamus of ovariectomized ewes treated with estradiol plus progesterone or with progesterone alone. Double-labeled cells were found throughout the medial POA, the periventricular part of the paraventricular nucleus (PVNpe), the arcuate nucleus (ARC) and the ventrolateral ventromedial nucleus (VMNvl). Colocalization ratios were not statistically different between steroid treatment groups. 84% of PR-immunoreactive cells in VMNvl, 90% in POA and ARC and 95% in PVNpe contain THRα. More than two-thirds of THRα-immunoreactive cells contain PR in each area examined. This study provides evidence that progesterone and thyroid hormones may act within the same cells to modulate physiological functions such as reproduction.
No Priming of the Immune Response in Newborn Brown Norway Rats Dosed with Ovalbumin in the Mouth
Authors: Madsen C. , Pilegaard K.
Published: April 2003

Background: Other researchers have reported that the specific immune response to subsequent antigen challenge is primed in newborn mice or rats dosed orally by gavage. We wanted to investigate if priming of a subsequent specific IgE response could be achieved by dosing newborn rats orally with ovalbumin and if this method could be used in an animal model for food allergy. Methods: Newborn Brown Norway rats were dosed with ovalbumin in the mouth (100 µg or 6 mg). As young adults, the animals were dosed by gavage for 35 days with 1 mg ovalbumin/day or once intraperitoneally with 100 µg. Control groups were dosed by gavage or intraperitoneally but not as neonates. Additionally, young adult rats were dosed with 1 mg ovalbumin/day in the mouth for 35 days. Sera from individual animals were analysed for specific IgE and specific IgG. Results: In all experiments with neonatal rats the specific IgE and IgG responses were decreased compared to the control groups, however, not always reaching statistical significance. A statistical significant decrease in the specific immune response was found in young adult rats dosed in the mouth as compared to by gavage. Conclusions: Dosing Brown Norway rats with ovalbumin in the mouth as neonates do not prime the specific immune response. The decrease in immune response found in our experiments when dosing newborn animals in the mouth in opposition to the priming seen by others when dosing by intragastric intubation may be explained by a dissimilar antigen presentation when dosing includes both oral mucosa and gut.
Induction of Basophil Desensitization in Physiological Medium: Enhancement after IgE-Dependent Upregulation of Surface IgE Binding on Basophils
Authors: Komiya Akiko , Hirai Koichi , Iikura Motoyasu , Nagase Hiroyuki , Yamada Hirokazu , Miyamasu Misato , Ohta Ken , Morita Yutaka , Ra Chisei , Yamamoto Kazuhiko , Yamaguchi Masao
Published: April 2003

Background: Although the ability of basophils to release mediators, called releasability, may be an important aspect which influences the proinflammatory role of these cells, clinical approaches aiming at the depletion of the releasability have not been established. We examined whether the desensitization procedure in Ca2+-containing physiological conditions can make basophils completely unresponsive to IgE-mediated stimulation, and whether basophil desensitization is affected by the surface IgE levels. Methods: Human peripheral blood basophils were cultured with low concentrations of anti-IgE antibody or recombinant mite allergen. Following culture, cells were stimulated and their histamine release was measured. Results: Culturing with mite allergen or anti-IgE antibody below threshold concentrations induced potent desensitization in basophils. The desensitizing effect of anti-IgE was dose- and time-dependent; IgE-dependent releasability was completely suppressed when basophils were incubated with a near-threshold concentration of anti-IgE for ≧4 h. In the continuous presence of subthreshold doses of anti-IgE, basophils remained desensitized even after 3 days. Basophils which had undergone an increase in surface IgE levels after 24-hour culture with IgE demonstrated enhanced desensitization. Conclusions: Near-threshold stimulation in physiological medium can affect basophils, thereby inducing complete and sustained deprivation of releasability without triggering degranulation. Basophil desensitization is regulated by their surface IgE levels. Induction of full desensitization may represent a potentially important therapeutic strategy for IgE-mediated allergic diseases in which basophils play pathogenic roles.
Positive Effects of a Fresh Air Filtration System on Hay Fever Symptoms
Authors: Brehler Randolf , Kütting Birgitta , Biel Klaus , Luger Thomas
Published: April 2003

Background: Avoidance of allergen exposure is the basic preventive measure in reducing symptoms of immediate-type allergies. As room air cleaners were found to have no benefic effect on general health, their use has not been recommended. The purpose of this study was to evaluate the effect of a fresh air filtration system installed in the bedrooms of non-air-conditioned homes on hay fever symptoms. Methods: In a placebo-controlled, double-blind, two-period, crossover study, we investigated the effectiveness of a fresh air filtration system installed in the bedrooms of volunteers suffering from hay fever. Results: Volunteers only suffering from pollinosis reported an improvement of their allergy symptoms. We observed a significant decrease in nighttime hay fever symptoms and an increase in morning peak expiratory flow rates (PEFR). No effects were recognized in volunteers who additionally had perennial allergy. Conclusion: Based upon these results, the installation of fresh air filtration systems in bedrooms should be recommended for patients suffering from hay fever.
Effects of Long-Term Oral Hormone Replacement Therapy on Plasma Nitric Oxide and Beta-Endorphin Levels in Postmenopausal Women
Authors: Akhan Süleyman Engin , Gürel Tülin , Has Recep , Iyibozkurt Ahmet Cem , Turfanda Abdullah
Published: April 2003

Objectives: The aim of this study is to evaluate the relationship between plasma nitric oxide (NO) and β-endorphin levels in women using hormone replacement therapy (HRT) for 12 months. Material and Methods: Our study group was composed of 55 patients who were in at least their second postmenopausal year. Of the 55 patients, 25 were in the control group. All 30 women in the study group received 2 mg 17β-estradiol + 1 mg norethisterone acetate tablets daily for 12 months. Plasma NO and β-endorphin levels were measured both before and after the study period and possible relationships were analyzed. Results: There was a significant increase in both β-endorphin (p = 0.0001, 10.93 ± 2.25 vs. 14.85 ± 2.49) and NO (p = 0.0001, 19.79 ± 4.01 vs. 27.83 ± 10.27) levels measured after the study in the HRT group. A correlation was seen between the increments in β-endorphin and NO levels in the HRT group. Conclusion: Continuous combined HRT raises both plasma NO and β-endorphin levels and a close relationship was found between the two molecules after therapy. We postulate that the increment in these molecules may explain some of the beneficial effects of HRT on cognitive function and mood.
Does the Introduction of New Technology Change Population Demographics? Minimally Invasive Technologies and Endometrial Polyps
Authors: Chavez Norma F. , Garner Elizabeth O. , Khan Wasim , Quade Bradley J. , Sharif Naba A. , Syed Fareeha , Stewart Elizabeth A.
Published: April 2003

Objective: To determine if the characteristics of women with endometrial polyps changed as minimally invasive modalities for diagnosis and surgical treatment were integrated to our clinical practice. Materials and Methods: The pathologic reports of all women diagnosed with endometrial polyps in 1990 (220 patients) and 1996 (386 patients) were reviewed. The respective medical records were reviewed for anthropomorphic factors, bleeding pattern, diagnosis, and modality of surgical removal. Comparisons of dichotomous data and analysis of nominal variables with two or more categories were carried out with the χ2 test. Results: Differences in patient characteristics or pattern of bleeding were minimal. In both groups, endometrial polyps were more frequent in women with abnormal bleeding, reaching almost 80%. Diagnostic and therapeutic modalities were significantly different in 1990 vs. 1996. Diagnosis by ultrasound increased fivefold (3.6 vs. 16.8%) and operative hysteroscopy increased threefold (6.4 vs. 19.7). The frequency of incidental diagnosis of endometrial polyps at the time of hysterectomy decreased significantly. The most frequent modality of surgery done in 1990 was dilatation and curettage (44.6%), followed in frequency by endometrial biopsy and abdominal hysterectomy. In contrast, the most frequent modality in 1996 was hysteroscopic resection (36.8%), followed by dilatation and curettage (12.8%). Conclusions: The introduction of minimally invasive methods of diagnosis and treatment of endometrial polyps has not changed the overall patient population with this lesion.
Preoperative Findings in Non-Gynecologic Carcinomas Metastasizing to the Ovaries
Authors: Kikkawa Fumitaka , Shibata Kiyosumi , Ino Kazuhiko , Nomura Seiji , Kajiyama Hiroaki , Suzuki Takahiro , Kawai Michiyasu , Mizutani Shigehiko
Published: April 2003

This study evaluated whether preoperative findings are useful prognostic indicators in patients with non-gynecologic carcinomas metastasizing to the ovaries. Fifty-three patients were analyzed. Primary sites of carcinoma were discovered after gynecologic surgery in 20 patients. In 10 patients, primary sites of carcinoma were discovered during gynecologic surgery. Thirty-one patients received surgery on the primary site before gynecologic surgery. The primary site could not be identified in 2 patients. The 5-year survival rate was 40.0% in patients, who underwent surgery on the primary site before gynecologic surgery. However, the 5-year survival rate was 12.2% in patients, who underwent surgery on the primary site during or after gynecologic surgery. The CEA level was significantly lower in the stomach primary group than in the intestine primary group. However, CA125 was the only marker significantly affecting survival. In comparison with primary ovarian carcinoma, the sensitivity of CEA was significantly higher for non-gynecologic ovarian carcinoma, while that of CA125 was significantly less sensitive for non-gynecologic ovarian carcinoma. In conclusion, the prognosis was better in patients, who had undergone resection of primary carcinoma before gynecologic surgery on non-gynecologic ovarian carcinoma. CEA is a useful marker to distinguish non-gynecologic from primary ovarian carcinoma, while CA125 is the only significant prognostic marker for non-gynecologic ovarian carcinoma.
A New Isoquinolinone Derivative with Noble Vasorelaxation Activity
Authors: Hsien Lin Chia , Shan Lin Mei , Hsiu Lin Ying , Ming Chen I. , Rong Lin Pen , Cheng Chen-Yu , Cheng Tsai Ming
Published: April 2003

The pharmacological effects of BDPBI (7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride) were tested on isolated endothelium-containing or denuded aorta of the guinea pig. BDPBI with the formula C27H24BrCl2N3O was synthesized starting with 3-isochromanone. In the endothelium-containing preparations of the aortic rings, phenylephrine (PHE; 10 µmol/l) elicited contracture and acetylcholine (ACh; 10 µmol/l) or BDPBI (0.01–10 µmol/l) elicited relaxation effects on the PHE-precontracted preparations. The BDPBI-elicited effect on the PHE-precontracted aortic rings was not altered in the presence of adrenergic blockers (propranolol or yohimbine; 1 µmol/l) or pretreated preparations with aspirin, indomethacin (10 µmol/l) or L-NAME (1 mmol/l). However, the relaxation effects of BDPBI were blocked if the preparations were pretreated with diphenhydramine (10 µmol/l) or chloropheniramine maleate (10 µmol/l). In contrast to lower concentrations of atropine (1 µmol/l), higher concentrations of atropine (30 µmol/l) did block the effects of BDPBI on the PHE-precontracted aortic rings. HTMT dimaleate (0.01–10 µmol/l), a histamine H1 receptor agonist, also elicited relaxation effects on the PHE-precontracted preparation, and the effects were blocked if the preparations were pretreated with diphenhydramine or chloropheniramine maleate. On isolated denuded aorta of the guinea pig, BDPBI did not elicit relaxation effects on the PHE-precontracted aortic rings. These results demonstrated that the vasorelaxation effect of BDPBI on PHE-precontracted aortic rings is partly dependent on the activation of a histaminergic receptor from the vascular endothelium. We suggested that BDPBI would be an effective vasorelaxant for cardiovascular systems.
Regeneration of Primary Sensory Neurons
Authors: Donnerer Josef
Published: April 2003

Primary sensory neurons have an inherent capacity for regeneration of their cut, crushed, or chemically lesioned axons. This capacity is displayed to a much greater extent after lesions of the peripheral axons than after lesions of their centrally directed axons. Additionally, the surrounding tissue determines to a significant extent the degree of recovery: whereas the peripheral nerve tissue provides neurotrophic support and a favorable environment for axonal growth, the central terminals of primary sensory neurons face a non-permissive and inhibitory glial tissue. Mechanical lesions of the peripheral axons of dorsal root ganglion (DRG) sensory neurons can be repaired by the intrinsic regenerative capacity of the neuron itself, when outgrowing axons from the proximal stump are able to transverse the tissue scar and reach the distal stump of the nerve. Bridging the gap with an autologous nerve graft or a short artificial graft filled with nerve growth factor (NGF) can improve recovery. Neurotoxic lesions of the axon terminals are effectively recovered by intermittent local or systemic NGF injections. A recovery from a diabetic sensory neuropathy probably requires the continuous delivery of NGF or additional neurotrophic factors. A recovery from a dorsal rhizotomy or from a dorsal column lesion can possibly be achieved by the concomitant transgene-mediated overexpression of neurotrophins, the transformation of the DRG neuron cells to a competence for regrowth, and the counteraction of the growth-inhibitory nature of the central nervous system tissue.
Neuronal Nitric Oxide Synthase Is Associated with Airway Obstruction in BALB/c Mice Exposed to Ozone
Authors: Jang An-Soo , Choi Inseon-S. , Lee Jong-Un
Published: April 2003

Background: The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in asthma is controversial. Objective: To investigate the role of NO in mice exposed to ozone, three known isoforms of NOS [inducible NOS (iNOS), neuronal NOS (nNOS), and endothelial NOS (eNOS)] were studied. Methods: The expression of iNOS, nNOS, and eNOS was determined in lung by Western blot analysis after exposure to filtered air and ozone (0.12, 0.5, 1 or 2 ppm) for 3 h. Using barometric whole-body plethysmography and increase in enhanced pause (Penh) as an index of airway obstruction, we measured airway responses to ozone exposure. Bronchoalveolar lavage (BAL) was performed. Nitrate and nitrite were measured using a modified Griess reaction. Results: The nitrate concentration in BAL fluid, which indicates the in vivo generation of NO in airways, from the ozone-exposed group was significantly greater than that from the group exposed to filtered air (631.0 ± 86.4 vs. 152.1 ± 16.9 µmol/l, p < 0.05). The nitrate concentration in BAL fluid was increased more in mice exposed to 2-ppm ozone than that in mice exposed to filtered air or 0.12-, 0.5-, or 1-ppm ozone. Increases in Penh after exposure to ozone or filtered air were significantly higher in the ozone-exposed groups than in the group exposed to filtered air (p < 0.01). Increases in Penh were dependent on the ozone concentration. Although the protein levels of eNOS and iNOS determined were within normal levels, the amount of nNOS protein was markedly elevated in airway tissue homogenates of the group exposed to 2-ppm ozone. Conclusion: These findings demonstrate that the nNOS isoform may be involved in airway obstruction in mice exposed to ozone.
The Heart in Human Dystrophinopathies
Authors: Finsterer Josef , Stöllberger Claudia
Published: April 2003

Dystrophinopathies are due to mutations in the dystrophin gene on chromosome Xp21.1 and comprise the allelic entities Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilative cardiomyopathy (XLDCM). In all three entities, the heart is affected to various degrees, depending on the stage of the disease and the type of the mutation (cardiac involvement, CI). The pathoanatomic evidence of CI in dystrophinopathies is the replacement of myocardium by connective tissue or fat. In DMD/BMD, the left ventricular posterobasal and lateral walls are most extensively affected, sparing the right ventricle and the atrium. Degree and dynamics of CI vary among the three entities. In DMD/BMD, CI usually remains subclinical in the early stages of the disease. Typical initial manifestations of CI in DMD/BMD are sinus tachycardia, tall R1 in V1, prominent Q in I, aVL, V6 or in II, III, and aVF, increased QT dispersion and possibly autonomic dysfunction. Initially, echocardiography is normal or shows regional wall motion abnormalities in areas of fibrosis. With spreading of fibrosis, left ventricular dysfunction and ventricular arrhythmias additionally occur. In the final stages of the disease, systolic function may lead to heart failure and sudden death. Subclinical or clinical CI is present in about 90% of the DMD/BMD patients but is the cause of death in only 20% of the DMD and 50% of the BMD patients. XLDCM is a rapidly progressive, almost exclusively myocardial disorder, starting in teenage males as heart failure due to dilative cardiomyopathy (CMP), leading to death from intractable heart failure within 1–2 years after diagnosis. Therapy of arrhythmias and CMP in all three disorders follows the established cardiological recommendations. Due to its protective effect, ACE inhibitors are recommended already at the early stages of the disease. β-Blockers may be an additional option if indicated.