bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for the Formation of a Steinstrasse after Shock Wave Lithotripsy
Authors: Soyupek Sedat , Armağan Abdullah , Koşar Alim , Serel T. Ahmet , Hoşcan M. Burak , Perk Hakkı , Oksay Taylan
Published: May 2005

Introduction: We studied the various stone, renal, and therapy factors that could affect steinstrasse formation after shock wave lithotripsy (SWL) to define their predictive value. Patients and Methods: Between May 1999 and September 2002, 563 patients were treated with a Stonelight V3 lithotriptor. A steinstrasse was recorded in 46 patients. All patient data, stone and renal characteristics, and data of SWL were reviewed. Statistical analyses of patients, stones, and therapy characteristics in correlation with the incidence of steinstrasse formation were performed to assign factors that had a significant impact on the formation of this complication. Results: The overall incidence of a steinstrasse was 8.17%. The steinstrasse was in the pelvic ureter in 84.3% of the cases, in the iliac ureter in 7.84% of them, and in pelvic and iliac ureter in 7.84% of the patients. The incidence of a steinstrasse significantly correlated with stone size and site. The incidence rates of a steinstrasse in renal stones <1 cm, 1–2 cm, and >2 cm were 4.46, 15.87, and 24.3% respectively. The incidence rates of this complication in ureteral stones <1 cm and 1–2 cm were 3.37 and 9.52%, respectively. The incidence rates of a steinstrasse in stones located in upper calices, middle calices, lower calices, and renal pelvis were 6.12, 10.52, 6.36, and 19.32%, respectively. Conclusions: Stone size and site are the significant factors predicting the formation of a steinstrasse. If a patient has a high probability of steinstrasse formation, close follow-up with early intervention or prophylactic pre-SWL ureteral stenting is indicated.
Should High-Grade Prostatic Intraepithelial Neoplasia Change Our Approach to Infravesical Obstruction?
Authors: Tunc Murat , Sanli Oner , Kandirali Engin , Tefekli Ahmet , Oktar Tayfun , Esen Tarik , Acar Omer , Uysal Veli
Published: May 2005

Objectives: To investigate whether coexistence of high-grade prostatic intraepithelial neoplasia (HPIN) should change our therapeutic approach to infravesical obstruction. Material and Methods: Of 505 patients who underwent sextant transrectal ultrasonography (TRUS)-guided prostate biopsy, 65 (12.8%) had HPIN and 29 of them underwent prostatectomy (23 transurethral resection of prostate (TURP), 6 open) due to obstructive urinary symptoms. Patients without carcinoma were followed up with semiannual prostate-specific antigen (PSA) and digital rectal examination. After a follow-up of 24.8 ± 11.0 months, 19 of 29 patients who accepted our call had another sextant biopsy. Results: Mean age and initial mean PSA values of 29 patients were 67.6 ± 6.7 years and 9.26 ± 5.91 ng/ml, respectively. The final pathological evaluation of the surgical specimens revealed 2 prostatic adenocarcinomas both in the TURP group. The remaining 27 (93.2%) patients were found to have benign prostatic hyperplasia (BPH) and their serum PSA levels declined from 9.26 ± 5.91 to 4.59 ± 2.0 ng/ml 3 months after prostatectomy. Of the 19 patients who had another biopsy with a mean PSA value of 4.06 ± 4.61 ng/ml, 15 and 4 of them had BPH and HPIN respectively. Conclusions: Our preliminary data indicate that the presence of HPIN on TRUS-guided biopsies is not a factor to delay an indicated surgical intervention for infravesical obstruction.
Does Ischemia-Induced Prostate Damage during Cardiac Surgery Involving Cardiopulmonary Bypass Cause Bladder Outlet Obstruction?
Authors: Guvel Sezgin , Turkoz Riza , Egilmez Tulga , Kilinc Ferhat , Yaycioglu Ozgur , Atalay Hakan , Ozkardes Hakan
Published: May 2005

Objective: This study sought to investigate whether ischemia-induced prostate damage during cardiac surgery involving cardiopulmonary bypass causes bladder outlet obstruction. Materials and Methods: The study involved 37 men who underwent elective cardiac surgery involving cardiopulmonary bypass. Prostate-specific antigen (PSA) levels were determined preoperatively (baseline) and on postoperative days 1, 5, and 30. In 4 cases, the PSA level after the operation was unchanged from the preoperative level, so these 4 men were excluded from the study. In the remaining 33 patients, symptoms of bladder outlet obstruction were assessed using the International Prostate Symptom Score. Each subject completed this test preoperatively and 3, 6 and 9 months postoperatively, and the means scores at these time points were compared. The effects of patient age, operative time, CPB time, and aortic clamping time on postoperative increases in PSA levels were investigated. Results: Thirty-three (89.2%) of the 37 men exhibited increased postoperative PSA levels compared to baseline. The mean PSA level for the 33 cases on day 5 was significantly higher than the baseline mean, but the mean levels on postoperative days 1 and 30 were comparable to baseline. Nine (24.3%) of the 33 men had postoperative PSA levels greater than 4.0 ng/dl (the upper normal limit). There was no significant difference between preoperative and postoperative International Prostate Symptom Scores. Conclusion: The study indicates that men’s PSA levels are, indeed, increased after cardiac surgery with cardiopulmonary bypass. However, in 9 months of follow-up, there was no association between this PSA rise and development of BOO, according to International Prostate Symptom Scores.
Is Bladder Cycling Useful in the Urodynamic Evaluation previous to Renal Transplantation?
Authors: Errando Carlos , Batista Jose E. , Caparros Joan , Araño Pedro , Villavicencio Humberto
Published: May 2005

Objectives: To evaluate the usefulness of bladder cycling (BC) in differentiating between urodynamic abnormalities due to reversible bladder dysfunction and those due to preexisting lower urinary tract (LUT) abnormalities, and to determine if BC increases the diagnostic yield of urodynamic investigations (UIs) in these patients. Methods: Eleven patients with oligoanuria (<300 ml/day) were evaluated with complete UIs. All cases showed low compliance (mean 6 ml/cm H2O) and low cystometric capacity (mean 146 ml) and were placed in a BC program. The indications for UIs were LUT symptoms in 2 patients, LUT abnormalities (myelodysplasia or urethral valves) in 3 patients, or the appearance of an extremely small bladder on cystogram (6 patients). BC was performed through a hypogastric catheter in an outpatient setting. UIs were repeated afterwards. Results: After BC, 5 patients (45%) continued to have low compliance (<8 ml/cm H2O) and 4 patients (36%) had normal UIs. In 2 cases (18%), a previously unrecognized obstruction was diagnosed. No patient with LUT symptoms or abnormalities had a normal UI after BC. Conversely, 4 of 6 patients in whom BC was indicated due to a small bladder on cystogram had normal UIs after BC. Conclusions: BC is useful in explaining whether high bladder pressure is due to dysfunction or to preexisting disorders, and thus indicating the proper surgery for correction. Suprapubic BC significantly increases bladder capacity thus increasing the diagnostic yield of the UI.
Tinea cruris in Routine Urology Practice
Authors: Arıdoğan I. Atilla , Ateş Aylin , İzol Volkan , İlkit Macit
Published: May 2005

Introduction: Tinea cruris is almost exclusively a male dermatophytosis. This infection is also sexually transmitted, and may cause epidemics in public areas such as common bathing facilities, dormitories and among military recruits. It has been aimed to investigate the prevalence and the causative agents of tinea cruris and tinea pedis in patients who were admitted to the Department of Urology with various pathologies. Materials and Methods: Direct microscopy and cultures of the epithelial scrapings were performed to identify the causative agent in patients who were admitted to the Department of Urology. Results: Out of a total of 155 cases examined, 39 (25.1%) were mycologically proven cases of dermatomycosis. In 11 (28.2%) of the patients tinea pedis, in 3 (7.7%) tinea cruris and in 10 (25.6%) Candida intertrigo were detected. In the remaining 15 (38.5%) cases, only direct microscopic examinations were found positive. The most common causative agent was Candida albicans (33.4%) followed by Trichophyton rubrum (29.1%), Trichophyton mentagrophytes var. interdigitale (29.1%), Candida glabrata (4.2%) and Candida tropicalis (4.2%).Conclusion: The investigation of genital dermatomycosis should be a part of routine urological examination and the clinical diagnosis should be confirmed by mycological methods.
Apoptosis in Non-Tumorous Adult Human Testis Tissue
Authors: Schmelz H.U. , Meiswinkel J. , Port M. , Hauck E.W. , Schwerer M.J. , Weidner W. , Sparwasser C. , Abend M.
Published: May 2005

Introduction: Apoptosis seems to play an important role in tumorigenesis, prognosis and therapy of testicular tumors. To understand its biological significance, it is importantto quantify the amount of apoptosis and to compare the rate of apoptosis to that of a normal, unaffected reference tissue. Usually tissue from the unaffected site of the testis in patients with testicular cancer or testis tissue from patients who underwent surgical castration due to prostate cancer is used as the reference tissue. However it is not known, if both tissues are equivocal with respect to their apoptotic index. The purpose of the study was to compare the two most often used reference tissues for the quantification of apoptosis in testicular tissues with regard to their apoptotic index. Materials and Methods: The apoptotic indices of both tissues were compared, using two standard apoptosis detection methods, i.e. in situ end labeling and a morphological approach. Results: The apoptotic index in testis tissue from patients who were surgically castrated for antihormonal treatment of prostate cancer was shown to be significantly higher than the apoptotic index of tumor free but tumor-associated testicular tissue of testis cancer patients. There was a strong relationship between the apoptotic index and the age of the patients. Conclusion: Although there might be genetic changes in the tumor-associated testicular tissue influencing the apoptotic index, it seems advisable to use tumor-associated tissue rather than testis tissue of patients with prostate cancer as the reference tissue, due to the significant age dependence of the apoptotic index.
Intravesical Heparin and Peripheral Neuromodulation on Interstitial Cystitis
Authors: Baykal Kadir , Şenkul Temuçin , Sen Bülent , Karademir Kenan , Adayener Cuneyt , Erden Dogan
Published: May 2005

Introduction: We wanted to evaluate the therapeutic effect of intravesical heparin and peripheral neuromodulation on patients with interstitial cystitis. Materials and Methods: From March 2002 to August 2003, 8 female and 2 male subjects conform to the NIDDK criteria and not responsive to the previous conventional treatments were included in the study. Wisconsin pain scores, maximal cystometric capacities, and night and day voiding frequencies were determined and these studies were repeated in the 2nd and 12th months of the treatment with 10,000 units intravesical heparin and peripheral neuromodulation. Frequency of the treatment was once a week during first 8 weeks, once in 2 weeks in the following 8 weeks, and once in 3 weeks four times. Then, it was decreased to once a month. Results: The mean follow-up period was 13 months (12–16 months). Day and night voiding frequency were significantly better in the 2nd and 12th months, when compared to pretreatment values. The Wisconsin pain scores were 62.5 ± 13.9% and 62.8 ± 15.2% in the 2nd and the 12th months, respectively. The average increase in the maximum cystometric capacity was 54.8 ± 27.4% and 52.5 ± 31.6% in the 2nd and the 12th months, respectively. Conclusions: Intravesical heparin and peripheral neuromodulation combination seems to be an alternative for patients with interstitial cystitis not responsive to other treatments.
Endourologic Management of Duodenal Calculi in Pancreas-Kidney Transplantation
Authors: Rha Koon H. , Varkarakis Ioannis M. , Ong Albert M. , Pinto Peter A. , Molmenti Ernesto P. , Jarrett Thomas W.
Published: May 2005

Duodenal stones formed during pancreas-kidney transplantation are usually associated with nonabsorbable sutures or staples. We report on the delayed formation of a struvite duodenal stone not attributed to foreign material, managed successfully with intracorporeal electrohydraulic lithotripsy.
Severe Hypospadias Associated with Robertsonian Translocation
Authors: Kilic Nizamettin , Balkan Emin , Saglam Halil , Yakut Tahsin , Dogruyol Hasan
Published: May 2005

In this study, we report a 3-year-old boy with severe scrotal hypospadias with Robertsonian translocation [45,XY,t(13q;14q)]. The patient was born at term with a low birth weight and hypospadias. There was no endocrinological abnormality. His father also has a balanced 13–14 Robertsonian translocation. Two-stage hypospadias repair was carried out. The presence of this chromosomal anomaly and hypospadias are unique to our patient, compared to others with the 45,XY,t(13q;14q) translocation. Although no such association has been reported so far, we thought that severe hypospadias in this case might be associated with this translocation.
Partial Normalization of Serum Brain-Derived Neurotrophic Factor in Remitted Patients after a Major Depressive Episode
Authors: Gervasoni Nicola , Aubry Jean-Michel , Bondolfi Guido , Osiek Christian , Schwald Michèle , Bertschy Gilles , Karege Félicien
Published: May 2005

We had previously reported decreased serum brain-derived neurotrophic factor (BDNF) levels in depressed patients. In the present study, we tested the hypothesis that antidepressant treatment would normalize serum BDNF levels, at least in a subgroup of patients. Major depressed patients (15 females and 11 males) diagnosed according to DSM-IV criteria and healthy controls (13 females and 13 males) participated in this study. Serum BDNF was assayed with the ELISA method for depressed and remitted patients and the severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. An analysis of variance showed that treatment had an effect [F(1, 24) = 4.46, p = 0.045] on the normalization of serum BDNF levels. We also found a correlation between the severity of depression (r = 0.51, p = 0.008), the pretreatment BDNF levels (r = 0.62, p = 0.001) and the difference in serum BDNF levels after antidepressant treatment. These results suggest that antidepressant treatment has a positive effect on serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.
Testosterone and Nandrolone Sensitization of Brain Anteroventral Area of Third Ventricle to Hypertonic NaCl-Induced Sympathetic Response
Authors: Rosa Francisco , Antequera Rafael , Vásquez José , Romero-Vecchione Eduardo , Martínez Angela
Published: May 2005

Androgenic steroids increase atherogenesis, thrombogenicity and endothelial dysfunction when administered in high doses, however their effects on NaCl sensitivity of the brain anteroventral area of the third ventricle (ΔV3V) have not been explored. Sprague-Dawley male rats were anesthetized with sodium pentobarbital (40 mg/kg) and the femoral intra-arterial blood pressure and heart rate monitored through a strain-gauge blood pressure transducer and tachograph. ΔV3V microinjections of (2 µl) 1.5 mol/l NaCl solution were done according to brain coordinates: AP = 7.0 mm, L = 1.0 mm, D = 7.5 mm through a 0.2-mm diameter stainless steel needle. The injection site was verified with 1.0 µl neutral red solution. Basal systolic blood pressure increased 37.6 and 39.6 mm Hg after testosterone (1 mg/kg/day for 20 days) and nandrolone (1 mg/kg/day for 20 days) treatment respectively; diastolic blood pressure also increased upon testosterone and nandrolone treatment in 36.4 and 53.1 mm Hg, respectively; basal heart rate did not change. Vasopressor response to 1.5 mol/l NaCl ΔV3V microinjection was higher in testosterone-treated rats; systolic blood pressure increased 56.0 vs. 28.3 control mm Hg; diastolic blood pressure increased 54.0 vs. 25 control mm Hg. This hypertensive response was 29% longer lasting in testosterone compared to vehicle-treated rats. The same pattern of ΔV3V sensitization to hypertonic NaCl was observed in nandrolone-treated rats. Blood lipid profile changed to a proatherogenic fashion upon testosterone and nandrolone long-term treatment; the plasma-free testosterone concentration increased from 4.9 ± 0.9 to 36.0 ±7.1 pg/ml with the same testosterone treatment schedule. In conclusion, long-term androgenic steroid treatment sensitizes the brain ΔV3V region to hypertonic NaCl which in turn conducts into a sympathetic vasopressor and heart rate-stimulating action.
Unexpected Effects of Nitric Oxide Synthase Inhibitors on Extracellular Nitrite Levels in the Hippocampus in vivo
Authors: Watts Jo , Whitton Peter S. , Pearce Brian
Published: May 2005

The aim of this study was to determine whether extracellular nitric oxide levels in the hippocampus of freely moving animals were reduced by the administration of nitric oxide synthase (NOS) inhibitors via a microdialysis probe. Our results show that extracellular nitrite levels were increased following the infusion of N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), in the case of the latter, the response was biphasic. In contrast, infusion of both inhibitors together resulted in a substantial reduction in nitrite when compared to control. More predictably, the infusion of NMDA elicited an increase in extracellular nitrite levels. This effect was biphasic, the second phase occurring some 3 h after the drug infusion period had ended. When NMDA was infused in the presence of L-NAME, no agonist-induced increase in nitrite production was recorded, in fact nitrite levels were found to decline to below control values. There was no immediate increase in nitrite levels when NMDA was infused in the presence of 7-NI, although this may have been partially obscured by the biphasic effect of the inhibitor. It did appear, however, that the second phase of the NMDA-induced response was attenuated by 7-NI. No NMDA-evoked increase in nitrite was evident when the agonist was infused in the presence of a combination of both inhibitors. We have no clear explanation for the data presented here but suggest that up-regulated activity of particular NOS isoforms might compensate for the inhibition of the other by a mechanism yet to be elucidated. In addition, we propose that caution be exercised when interpreting results from in vivo microdialysis studies where NOS inhibitors are administered directly into the brain via a probe.
Lysophosphatidic Acid Induces Histamine Release from Mast Cells and Skin Fragments
Authors: Hashimoto Terumasa , Ohata Hisayuki , Momose Kazutaka , Honda Kazuo
Published: May 2005

The present study examined whether lysophosphatidic acid (LPA) induces histamine release and the role of Rho-associated protein kinase (ROCK) in histamine release utilizing Y-27632, an inhibitor of ROCK. Rat peritoneal mast cells and mouse skin fragments were challenged with LPA; subsequently, histamine contents were measured by spectrofluorometric assay. LPA-induced histamine release from mast cells and skin fragments occurred in a time- and dose-dependent manner Pretreatment with Y-27632 inhibited LPA-induced histamine release in a dose-dependent fashion. LPA-induced histamine release was not influenced by calcium-free conditions; however, A23187-induced histamine release decreased significantly. TMB-8, an intracellular calcium antagonist, dose-dependently inhibited the histamine release under these conditions. Additionally, Y-27632 scarcely affected A23187-induced histamine release. These findings suggest that LPA-induced histamine release may be attributable to calcium release from intracellular stores. Moreover, ROCK participates in the extracellular calcium-independent process of LPA-induced histamine release.
Ovalbumin-Induced IL-4, IL-5 and IFN-γProduction in Infants with Atopic Dermatitis
Authors: Kimura Mitsuaki , Obi Makiko
Published: May 2005

Background: Although hen’s eggs are considered a cause of infantile atopic dermatitis (AD), little is known about cytokine production upon egg stimulation in infants with AD. Objective: This study aimed to characterize the production of IL-4, IL-5 and IFN-γ upon stimulation with ovalbumin (OVA), a representative allergenic protein of egg, in infants with AD. Methods: Peripheral blood mononuclear cells (PBMCs) from 68 children with AD, including 46 infants (<1 year), were stimulated with OVA and the production of IL-4, IL-5 and IFN-γ was measured with ELISA kits. Results: Upon stimulation with OVA, the production of IL-4 and IL-5, but not IFN-γ, by PBMCs was significantly higher in infants with AD than in non-atopic controls. OVA-induced IL-5 production peaked in younger infants (2–5 months) and then decreased with age increase. In contrast, OVA-induced IL-4 production peaked at the age of 1–2. This coincided with the serum level of egg white-specific IgE (EW-IgE). There was a significant positive correlation between IL-5 production and the severity of symptoms in infants with AD, while IL-4 production significantly correlated with the serum level of EW-IgE. Conclusion: These results demonstrate that OVA-induced IL-5 production fluctuates with age in a different manner than IL-4 or EW-IgE. Our results suggest that egg contributes to the development of AD in younger infants by inducing the production of IL-5, but not IL-4.
Human Hair: An Unexpected Source of Cat Allergen Exposure
Authors: Liccardi Gennaro , Barber Domingo , Russo Maria , D’Amato Maria , D’Amato Gennaro
Published: May 2005

Background: Cat allergens are ubiquitous because the clothing of cat owners constitutes an important source of distribution of Fel d 1 in cat-free environments. Since Fel d 1 can adhere to a variety of surfaces, we sought to verify if human hair belonging to individuals with or without a cat at home might represent a reservoir and be a possible carrier of cat allergens. Methods: Seventy-three women (25 with a non-neutered male cat and 25 with a dog at home, and 23 controls without any direct contact with these animals) were recruited. The collection of material from hair was carried out using a modified version of a battery-powdered portable sampler. Particulate material was harvested onto glass fiber filters (25 mm in diameter, with a pore size of 2 µm; AP 20 Millipore, Milan Italy), extracted in phosphate buffer with BSA and then assayed for the evaluation of cat allergen using an ELISA based on anti-Fel d 1 monoclonal antibody. Results: Detectable levels of cat allergen were found in 2 controls, in 2 women with a dog at home and in 13 women with a cat at home, respectively. Conclusions: In some women with a cat at home, hair constitutes a significant reservoir of Fel d 1. It is likely that these amounts of cat allergen might contribute to allergic sensitization when released in cat-free environments.
Celecoxib Tolerability in Patients with Hypersensitivity (Mainly Cutaneous Reactions) to Nonsteroidal Anti-Inflammatory Drugs
Authors: Viola Marinella , Quaratino Donato , Gaeta Francesco , Caringi Mario , Valluzzi Rocco , Caruso Cristiano , Volpetti Sabrina , Romano Antonino
Published: May 2005

Background: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed in clinical practice, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem for both general practitioners and allergists. Methods: We assessed 120 patients (83 women and 37 men) who had experienced adverse reactions to one or more NSAIDs; 64 (53.3%) of them had reacted to only one NSAID (single reactors) and 56 (46.7%) to multiple NSAIDs (multiple reactors). Among our subjects, 76.7% reported cutaneous reactions, 8.3% respiratory symptoms, 10.8% both cutaneous and respiratory symptoms, and 4.2% anaphylaxis. All patients were subjected to a single-blind, placebo-controlled oral challenge with two different doses of celecoxib (50 + 150 mg 1 h later = cumulative dose of 200 mg). Results: None of the patients reacted to the placebo and only one (0.8%) suffered a reaction (urticaria) after the second dose of celecoxib. Conclusions: Celecoxib showed a 98.9% rate of tolerability in the 92 patients with exclusively cutaneous reactions and was well tolerated by all 28 subjects with NSAID-related respiratory or anaphylactic symptoms.
Breastfeeding and Atherosclerosis
Authors: Martin Richard M. , Ebrahim Shah , Griffin Maura , Smith George Davey , Nicolaides Andrew N. , Georgiou Niki , Watson Simone , Frankel Stephen , Holly Jeff M.P. , Gunnell David
Published: May 2005

Objectives—

The impact of breastfeeding in infancy on cardiovascular disease risk is uncertain. We related breastfeeding in infancy to atherosclerosis in adulthood.

Methods and Results—

A historic cohort study based on a 65-year follow-up of the Carnegie (Boyd Orr) survey of diet and health in prewar Britain, 1937 to 1939. A total of 732 eligible cohort members living in or around Aberdeen, Bristol, Dundee, Wisbech, and London were invited for follow-up examinations in 2002, and 405 (55%) participated. In models controlling for age and sex, breastfeeding was inversely associated with common carotid intima-media thickness (IMT; difference −0.03 mm; 95% CI, −0.07 to 0.01), bifurcation IMT (difference −0.19 mm; 95% CI, −0.37 to −0.01), carotid plaque (odds ratio [OR], 0.52; 95% CI, 0.29 to 0.92), and femoral plaque (OR, 0.54; 95% CI, 0.26 to 1.12), compared with bottle-feeding. Controlling for socioeconomic variables in childhood and adulthood, smoking and alcohol made little difference to effect estimates. Controlling for factors potentially on the causal pathway (blood pressure, adiposity, cholesterol, insulin resistance, and C-reactive protein) made little difference to observed associations.

Conclusions—

Breastfeeding may be associated with a reduced risk of atherosclerosis in later life. Measurement error and power considerations limit the extent to which conclusions about the mechanisms underlying this relationship can be made.
The Antiviral Cytomegalovirus Inducible Gene 5/Viperin Is Expressed in Atherosclerosis and Regulated by Proinflammatory Agents
Authors: Olofsson P.S. , Jatta K. , Wågsäter D. , Gredmark S. , Hedin U. , Paulsson-Berne G. , Söderberg-Nauclér C. , Hansson G.K. , Sirsjö A.
Published: May 2005

Objective—

Inflammatory processes play an important role in atherosclerosis, and increasing evidence implies that microbial pathogens and proinflammatory cytokines are involved in the development and activation of atherosclerotic lesions. To find new inflammatory genes, we explored the vascular transcriptional response to an activator of innate immunity bacterial lipopolysaccharides (LPSs).

Methods and Results—

Gene arrays identified the cytomegalovirus-inducible gene 5 (cig5)/viperin among the genes most potently induced by LPS in human vascular biopsies. Viperin was expressed by endothelial cells in atherosclerotic arteries and significantly elevated in atherosclerotic compared with normal arteries. In culture, cytomegalovirus infection, interferon-γ, and LPS induced viperin expression.

Conclusion—

Viperin is expressed in atherosclerosis and induced in vascular cells by inflammatory stimuli and cytomegalovirus infection. The putative functions of viperin in atherosclerosis may relate to disease-associated microbes.
Blood Oxygen Level–Dependent MRI of Tissue Oxygenation
Authors: Utz Wolfgang , Jordan Jens , Niendorf Thoralf , Stoffels Mandy , Luft Friedrich C. , Dietz Rainer , Friedrich Matthias G.
Published: May 2005

Objectives—

The contribution of endothelial function to tissue oxygenation is not well understood. Muscle blood oxygen level–dependent MRI (BOLD MRI) provides data largely dependent on hemoglobin (Hb) oxygenation. We used BOLD MRI to assess endothelium-dependent signal intensity (SI) changes.

Methods and Results—

We investigated mean BOLD SI changes in the forearm musculature using a gradient-echo technique at 1.5 T in 9 healthy subjects who underwent a protocol of repeated acetylcholine infusions at 2 different doses (16 and 64 μg/min) and
N
G
-monomethyl-
l
-arginine (
l
-NMMA; 5 mg/min) into the brachial artery. Sodium nitroprusside was used as a control substance. For additional correlation with standard methods, the same protocol was repeated, and forearm blood flow was measured by strain gauge plethysmography. We obtained a significant increase in BOLD SI during acetylcholine infusion (64 μg/min) and a significant decrease for
l
-NMMA infusion (
P
<0.005 for both). BOLD SI showed a different kinetic signal than did blood flow, particularly after intermittent ischemia and at high flow rates.

Conclusions—

In standard endothelial function tests, BOLD MRI detects a dissociation of tissue Hb oxygenation from blood flow. BOLD MRI may be a useful adjunct in assessing endothelial function.
Platelet Microparticles
Authors: Mause Sebastian F. , von Hundelshausen Philipp , Zernecke Alma , Koenen Rory R. , Weber Christian
Published: May 2005

Objective—

Platelet activation mediates multiple cellular responses, including secretion of chemokines such as RANTES (CCL5), and formation of platelet microparticles (PMPs). We studied the role of PMPs in delivering RANTES and promoting monocyte recruitment.

Methods and Results—

Here we show that PMPs contain substantial amounts of RANTES and deposit RANTES on activated endothelium or murine atherosclerotic carotid arteries. RANTES deposition is facilitated by flow conditions and more efficient than that conferred by PMP supernatants. Interactions of PMPs with activated endothelium in flow were mostly characterized by rolling. RANTES deposition showed a diffuse distribution pattern and was rarely colocalized with firmly adherent PMPs, substantiating that RANTES deposition occurs during transient interactions. Importantly, preperfusion with PMPs enhanced monocyte arrest on activated endothelium or atherosclerotic carotid arteries, which could be inhibited by a blocking antibody or a RANTES receptor antagonist. Blockade or deficiency of PMP-expressed adhesion receptors demonstrated differential requirement of P-selectin, glycoprotein Ib (GPIb), GPIIb/IIIa, and junctional adhesion molecule-A for PMP interactions with endothelium, PMP-dependent RANTES deposition, and subsequent monocyte arrest.

Conclusion—

Circulating PMPs may serve as a finely tuned transcellular delivery system for RANTES, triggering monocyte arrest to inflamed and atherosclerotic endothelium, introducing a novel mechanism for platelet-dependent monocyte recruitment in inflammation and atherosclerosis.
GLUT4 Facilitative Glucose Transporter Specifically and Differentially Contributes to Agonist-Induced Vascular Reactivity in Mouse Aorta
Authors: Park James L. , Loberg Robert D. , Duquaine Damon , Zhang Hongyu , Deo Baljit K. , Ardanaz Noelia , Coyle Jami , Atkins Kevin B. , Schin MaryLee , Charron Maureen J. , Kumagai Arno K. , Pagano Patrick J. , Brosius Frank C.
Published: May 2005

Objective—

We hypothesized that GLUT4 is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction.

Methods and Results—

Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, ≈50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F
2α
-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT–mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4.

Conclusions—

Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.
Overexpression of VEGF-C Causes Transient Lymphatic Hyperplasia but Not Increased Lymphangiogenesis in Regenerating Skin
Authors: Goldman Jeremy , Le Thomas X. , Skobe Mihaela , Swartz Melody A.
Published: May 2005

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis and holds potential for lymphangiogenic therapy in diseases lacking adequate lymphatic drainage. However, the ability of VEGF-C to enhance sustainable, functional lymphatic growth in adult tissues remains unclear. To address this, we evaluated VEGF-C overexpression in adult lymphangiogenesis in regenerating skin. We used a model of mouse tail skin regeneration incorporating a suspension of either VEGF-C overexpressing tumor cells, which provide a continuous supplement of excess VEGF-C to the natural regenerating environment for more than 25 days, or otherwise identical control-transfected tumor cells. We found that excess VEGF-C did not enhance the rate of lymphatic endothelial cell (LEC) migration, the density of lymphatic vessels, or the rate of functionality - even though lymphatic hyperplasia was present early on. Furthermore, the hyperplasia disappeared when VEGF-C levels diminished, which occurred after 25 days, rendering the lymphatics indistinguishable from those in control groups. In vitro, we showed that whereas cell-derived VEGF-C could induce chemoattraction of LECs across a membrane (which involves amoeboid-like transmigration), it did not increase LEC chemoinvasion within a 3-dimensional fibrin matrix (which requires proteolytic migration). These results suggest that whereas excess VEGF-C may enhance early LEC proliferation and cause lymphatic vessel hyperplasia, it does not augment the physiological rate of migration or functionality, and by itself cannot sustain any lasting effects on lymphatic size, density, or organization in regenerating adult skin.
Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor
Authors: Cerrone Marina , Colombi Barbara , Santoro Massimo , di Barletta Marina Raffaele , Scelsi Mario , Villani Laura , Napolitano Carlo , Priori Silvia G
Published: May 2005

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the
RyR2
gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR
R4496C
) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR
R4496C
mice (
P
=0.02). Twenty-one mice (8 WT, 8 RyR
R4496C
, and 5 RyR
R4496C
pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR
R4496C
mice but none of the WT developed VT (
P
=0.02); 4/5 RyR
R4496C
mice pretreated with propranolol developed VT (
P
=0.56 nonsignificant versus RyR
R4496C
mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.
Virtual Reality–Induced Cortical Reorganization and Associated Locomotor Recovery in Chronic Stroke
Authors: You Sung H. , Jang Sung Ho , Kim Yun-Hee , Hallett Mark , Ahn Sang Ho , Kwon Yong-Hyun , Kim Joong Hwi , Lee Mi Young
Published: May 2005

Background and Purpose—

Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients.

Methods—

Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI (fMRI) and standardized locomotor tests, respectively. The
t
test and nonparametric test were performed to compare the mean differences at
P
<0.05.

Results—

There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups (
P
<0.05), indicating that VR practice produced a greater increase in LI for the control group. However, the interval changes in the other ROIs were not significantly different (
P
>0.05). Motor function was significantly improved after VR (
P
<0.05).

Conclusions—

Our novel findings suggest that VR could induce cortical reorganization from aberrant ipsilateral to contralateral SMC activation. This enhanced cortical reorganization might play an important role in recovery of locomotor function in patients with chronic stroke. This is the first fMRI study in the literature that provides evidence for neuroplasticity and associated locomotor recovery after VR.
Aggressive Therapy With Intravenous Abciximab and Intra-Arterial rtPA and Additional PTA/Stenting Improves Clinical Outcome in Acute Vertebrobasilar Occlusion
Authors: Eckert Bernd , Koch Christoph , Thomalla Götz , Kucinski Thomas , Grzyska Ulrich , Roether Joachim , Alfke Karsten , Jansen Olav , Zeumer Herrmann
Published: May 2005

Background and Purpose—

A combined therapy of local recombinant tissue plasminogen activator (rtPA) fibrinolysis and intravenous Abciximab platelet inhibition with additional percutaneous transluminal angioplasty (PTA)/stenting may improve recanalization and neurological outcome in patients with acute vertebrobasilar occlusion.

MethodsCombined FAST therapy consisted on intravenous bolus of Abciximab (0.25 mg/kg) followed by a 12-hour infusion therapy (0.125 μg/kg per minute) and low-dose intra-arterial rtPA (median dosage: 20 mg, FAST cohort: N=47). The results were compared with a retrospective cohort, treated by intraarterial rtPA monotherapy (median dosage: 40 mg, rtPA cohort, N=41). Additional PTA/stenting was performed in case of severe residual stenosis. Recanalization success was classified according to the Trials in Myocardial Infarction (TIMI) criteria: TIMI0/1, failed recanalization; TIMI2/3, successful recanalization. Bleeding complications were evaluated according to severe extracerebral hemorrhage (ECH), asymptomatic intracerebral hemorrhage (AIH), and symptomatic intracerebral hemorrhage (SIH).

Results—

Overall bleeding rate was higher under the combined therapy, but the SIH rate did not differ (FAST versus rtPA: ECH, 3% versus 0%; AIH, 32% versus 22%; SIH 13% versus 12%). Additional PTA/stenting was performed in 14 (FAST) versus 5 (rtPA) patients. TIMI2/3 recanalization rate was similar (FAST, 72%; rtPA, 68%), but TIMI3 rate was remarkably higher under combined therapy (FAST, 45%; rtPA, N=22%). Neurologic outcome appeared better under combined therapy (FAST versus rtPA: favorable outcome rate: 34% versus 17%) with a significantly lower mortality rate (FAST versus rtPA: 38% versus 68%;
P
=0.006). These results were consistent for embolic and atherothrombotic occlusions.

Conclusion—

Combined therapy of intravenous Abciximab and half dose intra-arterial rtPA with additional PTA/stenting appears to improve neurologic outcome in acute vertebrobasilar occlusion despite an increase of overall bleeding complications.
Active Finger Extension Predicts Outcomes After Constraint-Induced Movement Therapy for Individuals With Hemiparesis After Stroke
Authors: Fritz Stacy L. , Light Kathye E. , Patterson Tara S. , Behrman Andrea L. , Davis Sandra B.
Published: May 2005

Background and Purpose—

Constraint-induced movement therapy (CIMT) is a rehabilitative strategy used primarily with the post-stroke population to increase the functional use of the neurologically weaker upper extremity through massed practice while restraining the lesser involved upper extremity. Whereas research evidence supports CIMT, limited evidence exists regarding the characteristics of individuals who benefit most from this intervention. The goal of this study was to investigate the potential of 5 measures to predict functional CIMT outcomes.

Methods—

A convenience sample of 55 individuals, >6 months after stroke, was recruited that met specific inclusion/exclusion criteria allowing for individuals whose upper extremity was mildly to severely involved. They participated in CIMT 6 hours per day. Pretest, post-test, and follow-up assessments were performed to assess the outcomes for the Wolf Motor Function Test (WMFT). The potential predictors were minimal motor criteria (active extension of the wrist and 3 fingers), active finger extension/grasp release, grip strength, Fugl–Meyer upper extremity motor score, and the Frenchay score. A step-wise regression analysis was used in which the potential predictors were entered in a linear regression model with simultaneous entry of the dependent variables’ pretest score as the covariate. Two regressions models were determined for the dependent variable, for immediate post-test, and for follow-up post-test.

Results—

Finger extension was the only significant predictor of WMFT outcomes.

Conclusions—

When using finger extension/grasp release as a predictor in the regression equations, one can predict individual’s follow-up scores for CIMT. This experiment provides the most comprehensive investigation of predictors of CIMT outcomes to date.
Screening for Obstructive Sleep Apnea in Stroke Patients
Authors: Brown Devin L. , Chervin Ronald D. , Hickenbottom Susan L. , Langa Kenneth M. , Morgenstern Lewis B.
Published: May 2005

Background and Purpose—

Obstructive sleep apnea (OSA) is common after acute ischemic stroke and predicts poor stroke recovery, but whether screening for OSA and treatment by continuous positive airway pressure (CPAP) improves neurological outcome is unknown. We used a cost-effectiveness model to estimate the magnitude of benefit that would be necessary to make polysomnography (PSG) and OSA treatment cost-effective in stroke patients.

Methods—

A decision tree modeled 2 alternative strategies: PSG followed by 3 months of CPAP for those found to have OSA versus no screening. The primary outcome was the utility gained through OSA screening and treatment in relation to 2 common willingness-to-pay thresholds of $50 000 and $100 000 per quality-adjusted life year (QALY).

Results—

Screening resulted in an incremental cost-effectiveness ratio of $49 421 per QALY. Screening is cost-effective as long as the treatment of stroke patients with OSA by CPAP improves patient utilities by >0.2 for a willingness-to-pay of $50 000 per QALY and 0.1 for a willingness-to-pay of $100 000 per QALY.

Conclusions—

A clinical trial assessing the effectiveness of CPAP in improving stroke outcome is warranted from a cost-effectiveness standpoint.
Gender Differences in Outcome of Conservatively Treated Patients With Asymptomatic High Grade Carotid Stenosis
Authors: Dick Petra , Sherif Camillo , Sabeti Schila , Amighi Jasmin , Minar Erich , Schillinger Martin
Published: May 2005

Background and Purpose—

Gender differences are currently becoming increasingly recognized as an important prognostic factor in patients with atherosclerotic disease. We investigated gender-related differences in vascular outcome and mortality of asymptomatic patients with high-grade internal carotid artery (ICA) stenosis.

Methods—

We enrolled 525 consecutive patients (325 males with a median age of 72 years and 200 females with a median age of 75 years) from a single center registry who were initially treated conservatively with respect to a neurologically asymptomatic ≥70% ICA stenosis. Patients were followed-up for a median of 38 months (interquartile range, 18 to 65) for major adverse cardiovascular, cerebral, and peripheral vascular events (MACE: combined end point including myocardial infarction, stroke, [partial] limb amputation, and death), vascular mortality, and all-cause mortality.

Results—

Cumulative MACE-free survival rates in males and females at 1, 3, and 5 years were 83%, 65%, 48% versus 85%, 73%, and 67% (
P
=0.004), respectively. Adjusted hazard ratios for MACE, vascular mortality, and all-cause mortality for males were 1.96 (
P
=0.016), 2.48 (
P
<0.001), and 1.70 (
P
=0.007) as compared with females, irrespective of age, vascular risk factors, comorbidities, and the individual risk status estimated by the American Society of Anesthesiologists (ASA) score.

Conclusion—

Male patients with high-grade carotid artery stenosis are at a considerably higher risk for poor outcome than their female counterparts. In particular, the risk for fatal vascular events is substantially increased in males.
Reduction of Diffusion-Weighted MRI Lesion Volume After Early Moderate Hypothermia in Ischemic Stroke
Authors: Berger Christian , Schramm Peter , Schwab Stefan
Published: May 2005

Background—

Large areas of restricted diffusion in the middle cerebral artery (MCA) territory are highly predictive of severe and potentially space-occupying MCA stroke. A reduction of diffusion-weighted MRI (DWI) lesions occurs in 20% to 40% of acute stroke patients with early reperfusion.

Methods—

We report of a patient with a severe stroke syndrome who was treated with early moderate hypothermia but not thrombolysis.

Results—

The initially large DWI deficit of the whole MCA territory contrasted to the relatively small final lesion restricted to the basal ganglia on MRI and computed tomography scan.

Conclusion—

This case describes an unexpected reduction of a DWI lesion after early moderate hypothermia and spontaneous recanalization 3 days after stroke onset. We discuss potential reasons for the unexpected DWI lesion reduction.