bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of Cytokine Gene Transfer in Corneal Endothelial Cells and Organ-Cultured Corneas Mediated by Liposomal Vehicles and Recombinant Adenovirus
Authors: Bertelmann Eckart , Ritter Thomas , Vogt Katrin , Reszka Regina , Hartmann Christian , Pleyer Uwe
Published: April 2003

Purpose: Gene transfer of immunoregulatory cytokines could contribute to reduce rejection of corneal grafts. The aim of our study was to examine the gene transfer efficiency of liposomal vehicles compared to adenoviral vectors for transferring the Epstein-Barr-virus-derived interleukin 10 homologue (viral IL-10, vIL-10) into corneal endothelial cells and organ-cultured human corneas (HC) in vitro. Method: To test liposomal efficiency, 2 lipid formulations (SP-Chol/DOPE 20/80 and DDAB/DOPE 30/70 in various concentrations) were complexed with a plasmid containing the vIL-10 cDNA in an eukaryotic expression vector (pcDSRα-BCRF-I). The complexes were transferred to (1) subconfluent bovine corneal endothelial cells (BCEC) after 1 passage and to (2) HC stored in organ culture. In addition, BCEC and HC were transduced with the recombinant adenoviral vector encoding for vIL-10 (AdvIL-10). Secretion of vIL-10 in the supernatants from both transfected BCEC and HC was measured by specific ELISA. Results: For gene transfer in BCEC, both transfection methods (liposomes and adenovirus) led to high secretion of vIL-10 [>2 ng/ml (liposomes) and <150 ng/ml (adenovirus) per 5,000 initially planted BCEC]. Expression levels in BCEC were dependent on the concentration of applied liposomes. For gene transfer in HC, only the adenoviral transduction technique achieved a high production of vIL-10, whereas liposomal transfection led only to low vIL-10 secretion (4.8 µg/ml vs. 95 pg/ml per quarter of cornea). Conclusion: For transfection of corneal endothelial cells in culture, liposomes can be considered as a safe and useful alternative method of gene transfer avoiding side-effects of viral vectors. However, for transfection of organ-cultured HC, adenoviral vectors are superior to liposomal vehicles.
Apolipoprotein D Expression in Retinoblastoma
Authors: Alvarez María L. , Barbón Juan J. , González Louis O. , Abelairas Jose , Boto Ana , Vizoso Francisco J.
Published: April 2003

The presence of apolipoprotein D (apoD) synthesis in brain suggests that this protein could play a major role in mediating neuronal degeneration and regeneration in the central nervous system (CNS). For instance, apoD is overexpressed in neural tissues in Niemann-Pick’s type C disease, after acute CNS injury and cerebral ischemia, Alzheimer’s disease and by a number of different tumors such as breast, prostate, ovarian and endometrial carcinomas. Recent data have raised the possibility that apoD expression could be a marker of cellular differentiation and growth arrest. By immunohistochemistry, we evaluated the tumoral expression of apoD in retinoblastoma, a tumor that results from malignant transformation of primitive retinal cells before final differentiation, and analyzed the possible relationship with clinicopathological parameters such as: age, sex, histological type, staging, local invasion, metastasis, preoperative or postoperative treatment and bilateral tumors. A total of eleven retinoblastomas (55%) showed apoD-positive immunostaining, but no significant correlation was found between apoD expression and patient or tumor characteristics.
Optineurin Gene Expression Level in Human Trabecular Meshwork Does Not Change in Response to Pressure Elevation
Authors: Kamphuis Willem , Schneemann Andrea
Published: April 2003

Mutations in the gene optineurin (OPTN) have been associated with primary-open angle glaucoma. Here we present a study on the level of OPTN gene expression in the human trabecular meshwork in response to increased perfusion pressure in the anterior chamber perfusion model of the human eye. Perfusion pressure was raised from 10 to 30 mm Hg for periods ranging between 1 and 24 h. OPTN transcript levels in the trabecular meshwork were determined using real-time quantitative polymerase chain reaction. The results show no statistically significant alteration of the OPTN transcript level after raising the pressure. Moreover, no changes were detected in the transcript levels of the 3 known OPTN isoforms. This result shows that enhanced pressure levels do not lead to rapid changes in gene expression levels of OPTN in human trabecular meshwork. This suggests that alterations in OPTN gene expression are not involved in the mechanisms regulating aqueous humor outflow after an increase in intraocular eye pressure.
Effects of Direct Hemoperfusion with a β2-Microglobulin Adsorption Column on Hypercytokinemia in Rats
Authors: Nakatani Tatsuya , Tsuchida Kenji , Fu Ontaku , Sugimura Kazunobu , Takemoto Yoshiaki
Published: April 2003

Background/Aim: Blood purification therapies have been clinically applied to treat the cytokine-induced pathological responses. The effects of direct hemoperfusion(DHP) with a β2-microglobulin (BMG) adsorption column on hypercytokinemia were investigated. Methods: A hypercytokinemia model was prepared by injecting lipopolysaccharide (LPS) into femoral veins of male Wistar rats weighing 250–400 g. The hypercytokinemic rats were connected to the DHP system using a small BMG adsorption column, and time course changes in plasma levels of inflammatory cytokines were then examined. Results: Plasma levels of interleukins (IL) 1β and 6 and tumor necrosis factor alpha (TNF-α) were found to be significantly elevated within 3 h after LPS injection in the control group that underwent extracorporeal circulation without the BMG adsorption column, whereas the increases in plasma levels of IL-6 and TNF-α were significantly inhibited in the group that was treated with the BMG adsorption column. The adsorption rates of cytokines with the BMG adsorption column were 20–40% for IL-1β and IL-6 and 10–85% for TNF-α during treatment for 3 h. Conclusions: These results suggest that the systemic inflammatory response syndrome with hypercytokinemia might be treated with DHP using the BMG adsorption column.
Die Sentinellymphknotenbiopsie beim Mammakarzinom
Authors: Reitsamer R. , Menzel C. , Peintinger F. , Cimpoca W. , Glück S. , Sinzinger G. , Rettenbacher L. , Kässmann H. , Hoffmann A. , Prokop E. , Strasser F. , Kiesler J. , Hutarew G. , Dietze O.
Published: April 2003

Einleitung: Seit der Einführung der Sentinellymphknotenbiopsie (SLNB) zum axillären Staging bei Mammakarzinompatientinnen hat sich diese Operationstechnik in den meisten Brustzentren etabliert. Die Idee, mit einem weniger invasiven Eingriff als der axillären Dissektion den Nodalstatus exakt zu evaluieren, ist faszinierend und entspricht dem Gesamtkonzept in der Behandlung des Mammakarzinoms, den operativen Eingriff so wenig invasiv wie möglich zu gestalten. An wenigen Abteilungen wurde bereits dazu übergegangen, bei negativem Sentinellymphknoten (SLN) auf die Axilladissektion zu verzichten. Patientinnen und Methode: Von März 1998 bis März 2002 wurde an unserer Abteilung an 500 Patientinnen mit invasivem Mammakarzinom die Technik der SLNB angewandt. Anfangs wurde die Axilladissektion direkt im Anschluss an die SLNB durchgeführt. Nach der Lernphase an 75 Patientinnen mit einer Sensitivität von 96,2% und einer falsch negativen Rate von 3,8%, wurde bei Patientinnen mit negativem SLN unter definierten Voraussetzungen auf eine Axilladissektion verzichtet. Zusätzlich wurde aber das Spektrum erweitert und die Methode bei Patientinnen mit multizentrischem Karzinom und bei Patientinnen nach neoadjuvanter Chemotherapie evaluiert. Zur Auffindung des SLN wurde die kombinierte Methode mit blauem Farbstoff und mit Technetium 99m markiertem Humanalbumin verwendet. Ergebnisse: 500 SLNB wurden durchgeführt. Die Detektionsrate für das gesamte Kollektiv betrug 86,2%. Nach Bereinigung der Patientinnen mit multizentrischem Karzinom und der Patientinnen nach neoadjuvanter Chemotherapie betrug die Detektionsrate 94,5%. Insgesamt war der SLN in 41,3% der Patientinnen positiv, in 58,7% der Patientinnen negativ. Diskussion: Die SLNB ist eine probate Alternative zur Axilladissektion bei Patientinnen mit Mammakarzinom unter definierten Voraussetzungen.
Hormonersatztherapie, besseres Altern, molekulargenetische Diagnostik und das Image des Frauenarztes
Authors: Schneider Henning
Published: April 2003

Während der therapeutische Nutzen der Hormonersatztherapie (HRT) für die Behandlung klimakterischer Beschwerden unbestritten ist, werden die Konsequenzen einer Langzeitverabreichung von Hormonen nicht zuletzt wegen der kürzlich publizierten Daten der Studie der «Women’s Health Initiative» durchaus kontrovers diskutiert. Die Vorstellung einer verbesserten Beschreibung eines Risikoprofils der einzelnen Frau durch molekulargenetische Untersuchungen klingt sehr verlockend, entbehrt leider jedoch bislang einer soliden wissenschaftlichen Grundlage. So gibt es bislang keine überzeugenden Daten, die zeigen, dass durch die Abstimmung der HRT auf ein individuelles Genprofil die Zahl der relativ häufigen leichten Nebenwirkungen oder der seltenen schweren Komplikationen reduziert werden kann. Die Zurückhaltung gegenüber Neuerungen in der Medizin, für die eine überzeugende Nutzen-Risiko-Bilanz nicht vorliegt, ist wichtiger Bestandteil der ärztlichen Verantwortung und damit auch ein ethisches Gebot.
Local Anesthetics Induce Human Renal Cell Apoptosis
Authors: Lee H. Thomas , Xu Hua , Siegel Cory D. , Krichevsky Igor E.
Published: April 2003

Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Local anesthetics induce apoptosis in neuronal and lymphocytic cell lines. We examined the effects of chronic (48 h) local anesthetic treatment (lidocaine, bupivacaine and tetracaine) on human proximal tubular (HK-2) cells. Apoptosis induction was assessed by detecting poly(ADP)-ribose polymerase fragmentation, caspase activation, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, DNA laddering and by cellular morphology. Cell death was quantified by measuring neutral red dye uptake and lactate dehydrogenase released into the cell culture medium. All 3 local anesthetics caused concentration-dependent cell death, induced HK-2 cell apoptosis and potentiated TNF-α induced apoptosis. Local anesthetics induced HK-2 cell apoptosis by activation of caspases 3, 6, 7, 8 and 9. ZVAD-fmk, a pan-caspase inhibitor, blocked the local anesthetic induced HK-2 cell apoptosis. Local anesthetics also inhibited the activities of anti-apoptotic kinases protein kinase B (Akt) and extracellular signal regulated mitrogen-activated protein kinase. Local anesthetic’s pro-apoptotic effects are independent of sodium channel inhibition as tetrodotoxin, a selective voltage-gated sodium channel blocker, failed to mimic local anesthetic-mediated induction or potentiation of HK-2 cell apoptosis. We conclude that local anesthetics induce human renal cell apoptotic signaling by caspase activation and via inhibition of pro-survival signaling pathways.
Increased Frequency of Islet Cell Antibodies in Unaffected Brothers of Children with Type 1 Diabetes
Authors: Eskola Vesa , Vähäsalo Paula , Åkerblom Hans K. , Knip Mikael
Published: April 2003

Aim: To assess the relation between islet cell antibody (ICA) positivity and demographic characteristics in an extensive series of first-degree relatives of children with type 1 diabetes (T1D). Methods: Family members of children diagnosed with T1D before the age of 16 years and attending one of 27 participating paediatric units in Finland taking care of children with diabetes were invited to volunteer for an ICA screening program aimed at identifying individuals eligible for inclusion in the European Nicotinamide Diabetes Intervention Trial (ENDIT). The final series comprised 2,522 first-degree relatives (1,107 males) with a mean age of 20.4 (range 0.1–51.9) years, out of whom 390 were fathers, 622 mothers, 717 brothers, and 793 sisters of affected cases. Results: Two hundred and four family members (8.1%) tested positive for ICA with levels ranging from 3 to 564 (median 18) Juvenile Diabetes Foundation (JDF) units. One hundred and five relatives (4.2%) had an ICA level of 18 JDF units or more. Males had detectable ICA more often than females (9.6 vs. 6.9%; p = 0.02). Antibody-positive family members under the age of 20 years had higher ICA levels than the older ones [median 18 (range 3–514) JDF units vs. 10 (range 3–564) JDF units; p = 0.008]. Among the adult relatives (≧20 years of age) antibody-positive females had higher ICA levels than the males [median 10 (range 5–564) JDF units vs. 9 (range 3–130) JDF units; p = 0.04]. Siblings had an increased frequency of high-titre ICA (≧18 JDF units) when compared to the parents (4.8 vs. 3.2%; p = 0.05). Among siblings, we found a higher frequency of ICA positivity in brothers than in sisters (10.8 vs. 6.9%; p = 0.01), and this was also true for high-titre ICA (6.0 vs. 3.8 %; p = 0.04). Geographically, the highest ICA prevalence was seen among relatives living in the middle of Finland (10.4 vs. 7.2% in the other parts of Finland; p = 0.01). Conclusions: These results imply that male gender and young age favour positive ICA reactivity among family members of children with T1D. Siblings test positive for high ICA titres (≧18 JDF units) more frequently than parents. Accordingly, judged from demographic characteristics, the yield of ICA screening in first-degree relatives would be maximized by targeting young brothers of affected cases.
Effects of Intra-Abdominal Drainages on Adhesion Formation and Prevention by Phospholipids in a Rat Model
Authors: Bertram P. , Treutner K.-H. , Tietze L. , Vicas M. , Weiss C. , Anurov M. , Titkova S. , Polivoda M. , Oettinger A.P. , Schumpelick V.
Published: April 2003

Background and Aims: The study was designed to asses the adhesiogenic capacity of silicone drainages and the protective effect of phospholipids (PL). Materials and Methods: A total of 75 Wistar rats were randomly assigned to the different groups. In a preliminary trial (pt; n = 15), all rats underwent midline laparotomy. The control group (Cpt; n = 5) received no further treatment. In the other animals, either an ‘easy flow’ drainage (EFpt; n = 5) or an ‘Aachen’ drainage (ACpt; n = 5) was placed into the abdominal cavity. In the final study (fs; n = 60), rats underwent laparotomy and colonic anastomosis. The control groups (Cfs) received no drainages. In the other groups either one of the two types of drainages (EFfs, ACfs) were introduced. In 50% of the rats, 75 mg/kg of PL were administered intraperitoneally (Cfs+PL, EFfs+PL, ACfs+PL). The other rats received no additional treatment (CfsØPL, EFfsØPL, ACfsØPL). All animals were sacrificed 10 days after surgery. Areas of adhesions and anastomotic bursting pressures were measured (mean ± SD). Results: In the preliminary trial, analysis of variance (ANOVA) revealed no differences between the groups after application of drainages (values are given in mean ± SD): Cpt mean 23.3 ± 29.4 mm2, EFpt 829.7 ± 679.3 mm2, ACpt 609.9 ± 219.4 mm2. In the final study, 2-factorial ANOVA showed a significant effect (p < 0.001) for the use of drainages but not for the application of PL (CfsØPL 140.6 ± 124.2 mm2, Cfs+PL 67.7 ± 60.4 mm2, EFfsØPL 1,217.0 ± 458.3 mm2, EFfs+PL 1,266.8 ± 368.3 mm2, ACfsØPL 861.7 ± 274.8 mm2, ACfs+PL 544.2 ± 193.8 mm2). Post hoc test for pairwise comparisons adjusted to Bonferroni showed significant differences (p < 0.001) between all of the three pairs (Cfs 104.1 ± 92.3 mm2 vs. EFfs 1,241.9 mm2 ± 413.3 mm2; Cfs vs. ACfs 702.9 mm ± 234.3 mm2; EFfs vs. ACfs). Discussion: The final study demonstrates the adhesiogenic capacity of silicone drainage tubes in combination with anastomoses. Any protective effect of PL alone or in combination with drainages could not be shown. Conclusions: Indication for the use of drainages in standard surgical procedures should be reconsidered within the scope of their potential to cause adhesions and subsequent complications.
Biotherapy with the Pineal Immunomodulating Hormone Melatonin versus Melatonin plus Aloe vera in Untreatable Advanced Solid Neoplasms
Authors: Lissoni Paolo , Giani Luisa , Zerbini Stanislao , Trabattoni Patrizia , Rovelli Franco
Published: April 2003

The possibility of natural cancer therapy has been recently suggested by advances in the knowledge of tumor immunobiology. Either cytokines such as IL-2, or neurohormones, such as the pineal indole melatonin (MLT), may activate anticancer immunity. In addition, immunomodulating substances have also been isolated from plants, particularly from Aloe vera. Preliminary clinical studies had already shown that MLT may induce some benefits in untreatable metastatic solid tumor patients, whereas, for the time being, no clinical trial has been performed with aloe products. We have carried out a clinical study to evaluate whether the concomitant administration of aloe may enhance the therapeutic results of MLT in patients with advanced solid tumors for whom no effective standard anticancer therapies are available. The study included 50 patients suffering from lung cancer, gastrointestinal tract tumors, breast cancer or brain glioblastoma, who were treated with MLT alone (20 mg/day orally in the dark period) or MLT plus A. vera tincture (1 ml twice/day). A partial response (PR) was achieved in 2/24 patients treated with MLT plus aloe and in none of the patients treated with MLT alone. Stable disease (SD) was achieved in 12/24 and in 7/26 patients treated with MLT plus aloe or MLT alone, respectively. Therefore, the percentage of nonprogressing patients (PR + SD) was significantly higher in the group treated with MLT plus aloe than in the MLT gorup (14/24 vs. 7/26, p < 0.05). The percent 1-year survival was significantly higher in patients treated with MLT plus aloe (9/24 vs. 4/26, p < 0.05). Both treatments were well tolerated. This preliminary study would suggest that natural cancer therapy with MLT plus A. vera extracts may produce some therapeutic benefits, at least in terms of stabilization of disease and survival, in patients with advanced solid tumors, for whom no other standard effective therapy is available.
Circadian Secretions of IL-2, IL-12, IL-6 and IL-10 in Relation to the Light/Dark Rhythm of the Pineal Hormone Melatonin in Healthy Humans
Authors: Lissoni Paolo , Rovelli Franco , Brivio Fernando , Brivio Orietta , Fumagalli Luca
Published: April 2003

It has been demonstrated that cytokine activities are under neuroendocrine control, recently mainly exerted by the pineal gland through the circadian secretion of its main hormone melatonin (MLT). It is mainly released during the night, but at present it is still unclear which relation exists between MLT and the circadian secretion of cytokines. This study was performed to evaluate the circadian secretion of IL-2, IL-6, IL-10 and IL-12 in relation to that of MLT. The study included 10 healthy volunteers whose venous blood samples were collected at 8 a.m., noon, 4 p.m., 8 p.m., 1 a.m. and 4 a.m. The mean levels of MLT were significantly higher during the night than during the light phase of the day. Similarly, IL-2 mean levels significantly increased during the night. IL-6 mean values were higher during the light period of the day without, however, any significant differences with respect to the nocturnal mean levels. Finally, no substantial circadian variation was seen in IL-10 and IL-12 mean concentrations. These results show that IL-2 secretion increases during the night, concomitantly to that of the pineal hormone MLT, whereas there is no evidence of a circadian secretion for the other cytokines. Since the pineal gland has been proven to stimulate IL-2 endogenous production, the nocturnal increase in IL-2 blood concentrations could depend at least in part on the promoting action of MLT, whose release increases during the dark period of the day.
Three-Dimensional Stapes Footplate Motion in Human Temporal Bones
Authors: Hato Naohito , Stenfelt Stefan , Goode Richard L.
Published: April 2003

The literature provides conflicting information on whether the motion of the stapes footplate is piston-like or some other type of motion, such as rotational or rocking. Examination of the three-dimensional (3D) motion of the stapes footplate appears to be an excellent way to understand this complicated motion. Five microsphere reflective targets were placed on the stapes footplate in ten fresh human cadaver temporal bone preparations, and their vibration measured through an extended facial recess approach using a laser Doppler vibrometer. The five target sites on the stapes footplate were center, anterior, posterior, superior and inferior. The stimulus was a sound input of 80–120 dB SPL at the tympanic membrane over a frequency range of 0.1 to 10 kHz. The 3D motion of the stapes footplate was calculated using the velocity amplitude and phase obtained for each target. For frequencies up to 1.0 kHz the vibration of the stapes footplate was primarily piston-like; this motion became complex at higher frequencies, with rotary motion along both the long and short axis of the footplate. When the cochlea was drained, stapes footplate motion became essentially piston-like for all frequencies.
The Clarion Electrode Positioner: Approximation to the Medial Wall and Current Focussing?
Authors: Mens Lucas H.M. , Boyle Patrick J. , Mulder Jef J.S.
Published: April 2003

In order to establish whether the electrical field created by a cochlear implant electrode is more focussed in a perimodiolar than in a medial position, voltages at non-stimulated electrodes were collected from the Clarion 1.2 implant before and after insertion of the Clarion Electrode Positioning System. The positioner is inserted lateral to the electrode array and is intended to bring the array close to the medial wall of the scala tympani. These intracochlear electrode voltages (IEVs) were collected in 9 surgeries with the HiFocus I electrode array with positioner. Stapedius reflex thresholds were decreased after insertion of the positioner on 20 out of 22 electrodes. Electrode impedances did not increase significantly. IEVs increased slightly for all stimulated electrodes. However, the positioner did not significantly affect the slope of the IEVs for any of the stimulated electrodes. Individual differences between patients in the mean IEV amplitude were considerable; 2 patients deafened by otosclerosis showed particularly low amplitudes. Thus, IEVs provided no evidence of a focussing of the electrical field by introducing the positioner. Possible benefits of a perimodiolar position regarding efficiency and channel separation are discussed in terms of a reduced distance between electrodes and neural elements.
A Double-Blind Randomised Placebo-Controlled Evaluation of Three Doses of Botulinum Toxin Type A (Dysport®) in the Treatment of Spastic Equinovarus Deformity after Stroke
Authors: Pittock S.J. , Moore A.P. , Hardiman O. , Ehler E. , Kovac M. , Bojakowski J. , al Khawaja I. , Brozman M. , Kaňovský P. , Skorometz A. , Slawek J. , Reichel G. , Stenner A. , Timerbaeva S. , Stelmasiak Z. , Zifko U.A. , Bhakta B. , Coxon E.
Published: April 2003

Background/Objectives: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport®) in post-stroke calf spasticity. Methods: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. Results: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002–0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators’ and patients’ assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. Conclusion: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.
Effects of Blood Pressure Lowering in the Acute Phase of Total Anterior Circulation Infarcts and Other Stroke Subtypes
Authors: Ahmed Niaz , Wahlgren Nils Gunnar
Published: April 2003

Background: Lowering of blood pressure (BP) in the acute phase of stroke is reported both to worsen and to improve the outcome. To investigate whether heterogeneity exists between stroke subtypes in the response to BP lowering, we analysed data from the Intravenous Nimodipine West European Stroke Trial (INWEST). Methods: INWEST enrolled acute ischaemic stroke patients within 24 h (n = 295) to the following groups: placebo (n = 100), 1 mg/h nimodipine (n = 101) or 2 mg/h nimodipine (n = 94). Patients were retrospectively classified as total anterior circulation infarct (TACI) (i.e. hemiparesis + hemianopia + dysphasia) and non-TACI (exclusion of any one of these). Main outcome measures were neurological (Orgogozo) and functional (Barthel) scores at day 21. Results: 106 patients were labelled as TACI and 62 as non-TACI. No significant difference in BP was observed between the TACI and non-TACI subtypes at baseline, nor did the subtypes differ in BP course within the treatment groups. A higher proportion of non-TACI patients received postrandomisation antihypertensive agents in addition to the study drug compared with TACI patients (55% non-TACI vs. 26% TACI, p < 0.005). For TACI patients, there was no outcome difference between the placebo- and nimodipine-treated groups. For non-TACI patients, placebo had a significantly better neurological (p = 0.004) and functional (p = 0.04) outcome than the high-dose nimodipine group. In multivariate analysis for TACI patients, BP reduction and nimodipine treatment had no relation with outcome. Baseline stroke severity (p < 0.005) was the only significant predictor of the outcome at day 21. For non-TACI patients, diastolic BP (DBP) reduction (p = 0.03) and nimodipine treatment (p = 0.001) were related to neurological deterioration and nimodipine treatment (p = 0.01) to functional deterioration. Systolic BP reduction was associated with neurological (p < 0.005) and functional improvement (p = 0.01). Baseline stroke severity (p < 0.005) was related to both neurological and functional outcome. Conclusion: BP lowering and nimodipine treatment had no significant effect on outcome for TACI patients. For non-TACI patients, DBP lowering worsened the neurological outcome and high-dose nimodipine worsened both the neurological and functional outcome.
A Community-Centric Internet Portal for Stereotactic and Functional Neurosurgery with a Probabilistic Functional Atlas
Authors: Nowinski Wieslaw L. , Belov Dmitry , Benabid Alim-Louis
Published: April 2003

Objective: This paper describes an Internet portal for stereotactic and functional neurosurgery with a probabilistic functional atlas (PFA) calculated from electrophysiological and neuroimaging data. This portal enables (1) data sharing among neurosurgeons; (2) the calculation of probabilistic functional maps of stereotactic target structures from a neurosurgeon’s own data, optionally combined with data from other neurosurgeons, and (3) the construction and development of a PFA of the human brain by the neurosurgical community via the Internet. Method: The overall approach is done in three steps: (1) development and validation of the algorithm for PFA generation; (2) design and development of the portal for stereotactic and functional neurosurgery with tools for the rapid calculation, presentation, and use of the PFA, and (3) portal testing with the initial data acquired for 274 Parkinson’s disease patients, 487 hemispheres, and 500 best contacts. This paper covers step 2 and some results from step 3. Results: The Internet portal has been developed in Java and tested with the available data. Functions have been developed for: (1) data input, transfer, and editing; (2) data selection for PFA generation; (3) PFA generation; (4) PFA display and interactive manipulation, and (5) target planning. The portal has been put on the Internet for public use and so far more than 100 users downloaded it. Conclusion: The Internet portal for stereotactic and functional neurosurgery with a PFA potentially increases both the accuracy of targeting and the neurosurgeon’s confidence. The portal may be useful for both experienced functional neurosurgeons who have studied numerous cases and novices in the field. The use of the PFA through this portal, and sharing and expanding its content by neurosurgeons represents a paradigm shift from manufacturer centric to community centric.
The Allergens of Parietaria
Authors: Colombo Paolo , Bonura Angela , Costa Maria Assunta , Izzo Vincenzo , Passantino Rosa , Locorotondo Giovanni , Amoroso Saverio , Geraci Domenico
Published: April 2003

Parietaria is a genus of dicotyledonous weeds of the Urticaceae family including several species and its pollen grain is one of the most important allergenic sources in the Mediterranean area. Species belonging to this genus induce IgE responses in approximately 10 million people. Identification of allergens by means of independent strategies suggest that the allergens of the two more common species, Parietaria judaica and Parietaria officinalis, show molecular weights ranging between 10 and 14 kD and that the allergens of the two extracts are highly cross-reactive. Biochemical analysis and molecular cloning allowed the isolation and immunological characterization of the two major allergens of the P. judaica pollen, Par j 1 and Par j 2. Sequence comparison suggests that the P j major allergens of P. judaica belong to the nonspecific lipid transfer protein family, and three-dimensional modeling by homology has revealed that both proteins present a very conserved structural motif composed of four α-helices. Immunological analysis has shown that Par j 1 and Par j 2 are able to bind most of the P. judaica-specific IgE and some of their IgE determinants have been mapped. Recombinant Par j 1 and Par j 2 allergens have been shown to possess immunological properties equivalent to their natural counterpart and their availability represents a fundamental tool for the diagnosis and therapy of Parietaria pollen allergy.
Offering Preconceptional Cystic Fibrosis Carrier Couple Screening in the Absence of Established Preconceptional Care Services
Authors: Henneman Lidewij , Bramsen Inge , van Kempen Linda , van Acker Manita B. , Pals Gerard , van der Horst Henriette E. , Adèr Herman J. , van der Ploeg Henk M. , ten Kate Leo P.
Published: April 2003

Objective: To investigate the feasibility and acceptability of different modes of offering preconceptional carrier screening for cystic fibrosis (CF) in the absence of established preconceptional care services. Methods: Individuals aged 20–35 years were invited by mail, either by the Municipal Health Services (MHS) or by their own general practitioner (GP) to participate in a screening program with their partner. Pretest education was provided either during a group educational session or during a GP consultation. The reasons given by participants and nonrespondents for (not) responding to the invitation for screening, sociodemographic characteristics, and their attitudes were assessed by means of questionnaires. Results: Of 38,114 individuals who received a first invitation, approximately 20% had a partner with whom they were planning to have children. The response rate, as measured by attendance at either a group educational session or a GP consultation, was not affected by whether the letter was sent by the MHS or the person’s GP. However, the response rate was about 2.5 times higher when the letter invited people to make an appointment with their GP for a consultation regarding CF carrier screening than when it invited them to attend an educational group session. A total of 559 couples (96%) consented to have the test after education. Repetition of the invitation increased the response. The main reason given by couples for not responding was ‘lack of time to attend’ or ‘forgot about it’ (48%). Another reason given was that they did not want to know their test results (28%). Eighty-nine percent of participants and 69% of nonrespondents believed that screening should be offered routinely to couples planning to have children. The GPs consulted (n = 18) reported no negative experiences, but due to the extra workload, 11 of them would not consider it to be part of their task. Conclusions: Among couples planning to have children, there is generally a positive attitude towards routinely offering population-based CF carrier screening. Preconceptional CF carrier screening appeared feasible, both in terms of practical achievements and target group accessibility. Participation varied according to the pretest education setting, with the primary care setting producing the highest rate of attendance.
Microalbuminuria Is Closely Related to Impaired Arterial Elasticity in Untreated Patients with Essential Hypertension
Authors: Tsioufis Costas , Tzioumis Costas , Marinakis Nikos , Toutouzas Konstantinos , Tousoulis Dimitrios , Kallikazaros Ioannis , Stefanadis Christodoulos , Toutouzas Pavlos
Published: April 2003

Background/Aim: Although an increase in urinary albumin excretion (UAE) and impaired arterial mechanics have both been identified as predictors of cardiovascular events in hypertensive subjects, the interaction between arterial pressure wave contour and microalbuminuria (MA) has not been well defined. Methods: MA was determined from three nonconsecutive 24-hour urine samples in a group of 130 untreated hypertensive subjects. The arterial pressure waveform was recorded by carotid artery applanation tonometry and expressed as the augmentation index (AIx), the ratio of the augmented pressure (the difference between the early and late systolic shoulder) to pulse pressure. The subjects were classified according to their arterial pressure waveform into type A (Aix >0.12), type B (0 < Aix ≤ 0.12), and type C (Aix ≤ 0). Results: Patients with MA (n = 48) were matched for demographics with those without MA (n = 82). Subjects with MA had significantly increased left ventricular mass index (101 vs. 85 g/m2, p < 0.0001), blood pressure (164/100 vs. 146/94 mm Hg, p < 0.005), and AIx (0.16 vs. 0.04, p < 0.03). Hypertensive patients with type A arterial pressure waveform had significantly increased values of the log 24-hour UAE as compared with those with type B and C pressure waveforms. The proportion of patients with type A waveform was significantly higher in microalbuminuric patients as compared with normoalbuminuric patients (67 vs. 33%, p < 0.005); in contrast, the proportion of patients with type B or C waveform was significantly higher in normoalbuminuric patients as compared with microalbuminuric patients (68 vs. 36%, p < 0.005). By multiple regression analysis and analysis of variance, it was revealed that an increased AIx was significantly and independently associated with increased values of UAE (p < 0.05). Conclusions: Hypertensive patients with MA exhibited an earlier systolic augmentation of the arterial pressure, reflecting a more impaired arterial elasticity as compared with hypertensive subjects without MA. These findings suggest that worse cardiovascular outcomes may be associated with the presence of an increased UAE in hypertensive subjects.
Paramnesic Multiplication of Autobiographical Memory as a Manifestation of Interictal Psychosis
Authors: Murai Toshiya , Fukao Kenjiro
Published: April 2003

This report describes a male patient with temporal lobe epilepsy who developed a persistent paranoid-hallucinatory state at the age of 23. The essential feature of his delusion was that he had repeatedly lived part of his life, namely between the ages of 21 and 25 years. The patient repeatedly attempted suicide to escape the endless repetition. His paramnesia has some similarity with a déjà vu phenomenon, which is a common ictal manifestation of temporal lobe epilepsy. However, while only a sense of vague familiarity is evoked in a déjà vu phenomenon, conscious recollection is experienced during his paramnesia. We attempted to explain the pathophysiological mechanism of the patient’s paramnesia in the framework of the current neurobiological theory of human memory.
Utility of the Combination of Echocardiography and Troponin T Test in Patients with ST Segment Depression
Authors: Di Pasquale Pietro , Paterna Salvatore
Published: April 2003

Background/Objective: In a cohort of patients with chest pain and a negative troponin T (TnT) test, a mortality rate of 1.4% during a mean follow-up of 9 weeks was recently reported. The mortality was greater in patients with evidence of ischemic ECG changes and a negative TnT test (1.6–4.4%). Few studies have examined the efficacy of two-dimensional echocardiography (2DE) in patients with chest pain. The purpose of the present study was to determine the clinical utility, sensitivity and specificity of the combination of TnT levels and 2DE in patients presenting with chest pain and ST depression on the entry ECG. Methods: 192 consecutive patients with chest pain and the presence of ST depression, an acceptable 2DE window, evidence or no evidence of alterations of the segmentary motion, a negative or positive TnT test and a normal value of creatine kinase (CK),CK-MB were enrolled. 2DE, blood CK,CK-MB and TnT levels were controlled at entry and subsequent samples were obtained every 4 h for the first 12 h and then every 12 h. A hemodynamic study was performed in all patients within 12–72 h of admission. Percutaneous transluminal coronary angioplasty or coronary artery bypass graft were performed according to angiographic findings and left ventricular function. Results: A total of 192 patients with ST segment depression met the entry criteria. The combination of positive TnT and wall motion alterations showed higher sensitivity, specificity and predictive values in comparison with TnT or 2DE alone. Patients with concordance between TnT and 2DE were at higher risk. Patients with a negative combination did not show the presence of critical coronary stenosis. The group with a negative 2DE (44 patients; 12.7%) had only 2 patients with critical coronary stenosis. Conclusion: Our results suggest that the combination of a negative TnT test and negative 2DE in patients presenting to the emergency department with chest pain and ECG changes is a useful tool to identify those who can be discharged safely. By using this combination we can identify the high-risk (when positive) patients and reduce the incidence of false negatives, but most importantly, it allows us to identify truly negative patients who can be discharged safely.
Prevalence of the Metabolic Syndrome: Impact on Cardiovascular Risk Epidemiology – A Population-Based Study from Malmö, Sweden
Authors: Nilsson Peter M. , Hedblad Bo
Published: April 2003

Background: The metabolic syndrome is an emerging risk factor complex of considerable importance for cardiovascular risk epidemiology. Insulin resistance is regarded as a key factor in this syndrome, which is also known as the insulin resistance syndrome (IRS). Epidemiological studies are needed to estimate the prevalence of the syndrome in various populations and subgroups based on gender or social/ethnic background, in order to be able to plan preventive measures. Objectives: To determine the prevalence and distribution of the metabolic syndrome/IRS and its association with social and ethnical background factors in middle-aged subjects. Methods: This was a cross-sectional case-control study carried out in Malmö, a city in southern Sweden. We included 4,567 subjects, born between 1926 and 1945, participating in a cohort study of diet and disease. The metabolic syndrome/IRS was defined as the presence of insulin resistance (by homeostasis model assessment in normoglycaemic subjects) together with two or more of the following variables: dyslipidaemia (i.e. elevated triglycerides or decreased high-density lipoprotein cholesterol), expanded waist circumference and hypertension. History of lifestyle, marital status, occupation, education level and ethnical background were assessed by a self-administered questionnaire. Results: The overall prevalence of the metabolic syndrome/IRS was 16.7%, with a strong relationship to age. After adjustments for age and sex, the presence of the metabolic syndrome/IRS was associated with the following factors: low physical activity [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2–1.7], high alcohol intake (OR 1.6, 95% CI 1.1–2.4), low educational level (OR 1.5, 95% CI 1.3–1.8), low social class (OR 1.5, 95% CI 1.3–1.8) and non-Swedish origin (OR 1.5, 95% CI 1.2–1.9). Conclusions: The distribution of the metabolic syndrome/IRS in the general population is influenced by lifestyle habits, sociodemographic factors and ethnical background.
Characteristics and Mechanisms of Isolated Rubella Virus, Strain JR23: Infection of the Central Nervous System of BALB/c Mice
Authors: Wang Zhiyu , Yao Ping , Song Yanyan , Wang Guiting , Wang Yongkang , Xu Hongzhi , Wang Peng
Published: April 2003

Objective: To investigate the correlation between rubella virus (RuV) antigen in peripheral lymphocytes, the immune status and RuV infection in the central nervous system (CNS). Methods: BALB/c mice were used as a model and treated with immunoaffecting medicines. Then, the mice were infected with RuV via the abdominal cavity, and the antigen level in peripheral lymphocytes was examined 1, 3, 7 and 14 days postinfection. RuV in the CNS was detected by immunohistochemical methods. BALB/c mice were given dexamethasone and cytoxan before infection with the RuV JR23 strain. Immune functions and RuV invasion of the CNS were assayed on day 21 postinfection via the abdominal cavity, and their relationship was analyzed. Results: The mean antigen detection rates at different times were 3.1, 4.1, 9.6 and 2.4%, respectively, in the dexamethasone group, and 14.2, 12.7, 9.9 and 3.1%, respectively, in the cytoxan group. In the group without any intervention, the detection rates were 4.63, 10.25, 6.88 and 1.75%, respectively. The antigen detection rates in peripheral lymphocytes among the three groups 24 h postinfection were significantly different (F = 0.0317, p < 0.05). Comparisons between groups showed that antigen detection rates in the cytoxan group were much higher than those in other groups, but there was no difference between the dexamethasone and control groups. The animals with persistent presence of antigen were much more susceptible to cerebral infection than those with short-term presence (p < 0.001). T cell functions of the cytoxan group were significantly lower than those of other groups (p < 0.05), as detected by the MTT method. Infection rates of the dexamethasone, cytoxan and control groups were 60, 90 and 50%, respectively. Cell immune functions of the mice with CNS infection were obviously worse than those of the mice without CNS infection (p < 0.001). RuV-specific antibodies were assayed in all groups by ELISA and the results showed that there were no significant differences among groups (p < 0.05) or between the groups with and without CNS infection. Conclusion: Cytoxan can affect virus detection rates in peripheral lymphocytes. At the early phase of infection, the persistent presence of RuV in peripheral lymphocytes increases the incidence of CNS infection. RuV infection in the CNS was related to the cell immune situation before specific antibody was produced in the body.
Genotype Analysis, Using PCR with Type-Specific Primers, of Hepatitis B Virus Isolates from Patients Coinfected with Hepatitis Delta Virus Genotype II from Miyako Island, Japan
Authors: Moriyama Mitsuhiko , Taira Masaaki , Matsumura Hiroshi , Aoki Hiroshi , Mikuni Morio , Kaneko Miki , Shioda Atsuo , Iwaguchi Kayo , Arai Shinobu , Ichijima Sagiri , Iwasaki Hiroko , Tanaka Naohide , Abe Kenji , Arakawa Yasuyuki
Published: April 2003

Objectives: The aims of this study were to determine the hepatitis B virus (HBV) genotypes in hepatitis delta virus (HDV) RNA-positive patients and to characterize the HBV nucleotide sequences that may be found on a distant island of Japan. Methods: This study included three patients with chronic hepatitis who were positive for hepatitis B surface antigen (enzyme-linked immunosorbent assay; ELISA), HDV antibody (ELISA) and HDV RNA by polymerase chain reaction (PCR). The HBV genotype was determined by nested PCR using type-specific primers. The first-round PCR products from two patients were sequenced, followed by an investigation of nucleotide homology. Results: Viruses from all three patients in this study were classified as HBV genotype B. Comparison with HBV isolates from geographically neighboring regions revealed that the two HBV isolates had 97.9–98.6% identity at the nucleotide level to a Chinese isolate, 98.3–98.6% identity to the Okinawa isolate and 98.6–98.8% identity to a Japanese isolate of genotype B. On phylogenetic analysis, the HBV isolates from the two patients were classified as HBV genotype B. The HBV isolates of cases 1 and 3 clustered in the same group as isolates from the Chinese mainland and Japanese mainland, which are geographically near Miyako Island. Conclusion: The HBV isolates coinfected with HDV found on Miyako Island were of genotype B. The PCR method based on genotype-specific primers was useful in determining HBV genotypes.
Palmitoleic Acid Isomer (C16:1Δ6) in Human Skin Sebum Is Effective against Gram-Positive Bacteria
Authors: Wille J.J. , Kydonieus A.
Published: April 2003

The percent lipid composition of pooled human sebum analyzed by thin-layer chromatography was: ceramides (13%), fatty acid (47%), cholesterol (7%), cholesterol esters (2%), squalene (11%), triglycerides (3%), and wax esters (17%). Total sebum lipids (2– 4 mg/ml), sonicated into bacterial culture medium, caused 4- to 5-fold log reduction in growth of gram-positive bacteria, Staphylococcus aureus, Streptococcus salivarius and the anaerobe Fusobacterium nucleatum, but was ineffective against most gram-negative bacteria. Fractionation of the sebum lipids showed that both saturated and unsaturated fatty acids contained the bulk of the antimicrobial activity. Lauric acid (C12:0) was the most active saturated fatty acid. The unsaturated fatty acid, palmitoleic acid (C16:1Δ6, cPA) was both the most predominant monoene and the most active antimicrobial fatty acid. Purified cPA (>99%) yielded typical minimal inhibitory concentration (MIC) values of 10–20 µg/ml against gram-positive bacteria. Organically synthesized cPA isomer gave MIC values comparable to the natural material. Both natural and synthetic cPA were found to be the most active sebum lipid fraction in blocking the adherence of a pathogenic strain of Candida albicans to porcine stratum corneum. Ethanol in combination with cPA exerts a synergistic bactericidal activity against gram-negative pathogenic bacteria, including Pseudomonas aeruginosa, Propionibacterium acnes, Escherichia coli, and several methacillin-resistant strains of S. aureus. Palmitoleic acid may be useful in topical formulations for treatment of secondary gram-positive bacterial infections, as a gram-positive bacteria antimicrobial in wound dressings, and as a natural gram-positive antimicrobial preservative in skin and hair care products.