bluuebunny/crossref_metadata_2025 huggingface dataset:
Lowering the PSA Threshold for Prostate Biopsy from 4 to 2.5 ng/ml: Influence on Cancer Characteristics and Number of Men Needed to Biopt
Authors: Müntener Michael , Kunz Urs , Eichler Klaus , Puhan Milo , Schmid Daniel M. , Sulser Tullio , Strebel Räto T.
Published: March 2010

Objective: In 1999 we lowered the prostate-specific antigen (PSA) threshold for prostate biopsy at our institution from 4 to 2.5 ng/ml. The aim of this study was to compare the differences in tumor characteristics of the detected prostate cancers (PCAs) and the detection rate for the two different PSA thresholds and to evaluate if lowering the threshold was justified by any of the detected differences. Patients and Methods: We retrospectively analyzed the records of all patients who underwent an 8-core prostate biopsy between January 1999 and December 2004 and had a PSA between 2.5 and 10 ng/ml. Patients with a PSA between 2.5 and 4 ng/ml (group 1, n = 214, mean age 62.0 years) were compared to patients whose PSA was between 4 and 10 ng/ml (group 2, n = 292, mean age 63.2 years). Patients who were older than 75 years or had a suspicious rectal examination were excluded from this study. Results: Overall, we detected 120 can-cers in 506 patients (cancer yield 23.7%). The cancer yield in group 1 was significantly lower than in group 2 (17 vs. 28%, p < 0.01). In group 1 significantly less Gleason score ≧7 (p = 0.04) and significantly more potentially insignificant cancers (p = 0.03) were identified. In 80 patients who subsequently underwent radical prostatectomy, final pathology revealed no significant differences between the two PSA groups with regard to high pT stages, Gleason score ≧7 PCA or positive surgical margins, respectively. The difference in the absolute risk of being diagnosed with high-grade PCA between a PSA threshold of 2.5 ng/ml and a PSA threshold of 4 ng/ml was 1%. Conclusion: Lowering the PSA threshold for prostate biopsy from 4 to 2.5 ng/ml results in a substantial increase in the number of men who undergo biopsy and may result in an increased detection of potentially insignificant cancers. If total PSA alone is used to determine the need for prostate biopsy, the disadvantages of this lower threshold probably outweigh its potential benefits.
Extended Biopsy Protocol Decreases Prostate Cancer Incidence and Risk of Aggressive Disease on Repeated Biopsies Compared with Initial Standard Procedure
Authors: Ploussard Guillaume , Bastien Laurence , Descazeaud Aurélien , Robert Grégoire , Allory Yves , Salomon Laurent , Vordos Dimitri , Hoznek Andreas , Yiou René , Abbou Claude-Clément , de la Taille Alexandre
Published: March 2010

Objectives: To compare prostate cancer detection rates in repeated biopsy depending on the number of cores at initial biopsy. Methods: Out of 3,000 consecutive patients, 534 underwent repeat extended biopsies. At first procedure, 345 patients had undergone standard biopsies (10–15 cores; SBx) whereas 189 other patients had already had a 21-core extended protocol (ExtBx). Clinicobiological and pathological parameters were compared between 2 groups. Results: The prostate cancer detection rate was significantly higher in the SBx group (37%) compared with the ExtBx group (16.8%, p < 0.001). Mean PSA level, mean percent free PSA and mean prostate volume were equivalent in both groups. Thirty-eight percent of cancers detected in the SBx group were graded Gleason 7 or more, compared with 19.3% in the ExtBx group (p = 0.018). Mean percent of core invasion was 25.3% in the SBx group compared to 15.9% in the ExtBx group (p = 0.004). Conclusions: A full evaluation of all prostate zones using ExtBx seems to be necessary to decrease the risk of undetected prostate cancer on repeated biopsies. For patients who had at their first biopsy an ExtBx, the risk of prostate cancer on the repeated biopsies and the risk of aggressive cancer were lower compared to standard biopsies.
Preoperative Prediction of Pathologically Insignificant Prostate Cancer in Radical Prostatectomy Specimens: The Role of Prostate Volume and the Number of Positive Cores
Authors: Raventós Carles X. , Orsola Anna , de Torres Inés , Cecchini Lluís , Trilla Enrique , Planas Jacques , Morote Joan
Published: March 2010

Introduction: To determine clinical and biopsy features with predictive capacity to identify pathologically insignificant prostate cancer (pIPCa). Material and Methods: pIPCa was defined as cancer volume <0.5 cm3 and a Gleason score (GS) of ≤6 in radical prostatectomy (RP) specimens. Clinical and biopsy parameters were studied as predictors of pIPCa and validated by applying them to d’Amico’s low-risk cases: T1c-T2a, prostate-specific antigen (PSA) <10 and biopsy GS ≤6. Appropriate cut-offs were selected. Results: 280 patients were evaluated; 11.8% (33) had pIPCa, increasing to 23% in low-risk cases. In patients fulfilling d’Amico’s low-risk criteria, variables significantly different in pIPCa were: volume, number of positive cylinders (NPC), percentage of positive cylinders (%PC), percentage of the most affected cylinder (%MAC) and uni/bilaterality. In these cases, volume and the NPC increased as independent variables on logistic regression and when adding a volume threshold of 45 cm3 and 1 positive core, specificity reached 95.8%. Conclusions: The incidence of pIPCa in RP specimens is relevant, especially in low-risk cases. Prostate volume and NPC are independent predictors of pIPCa. We propose a simple predictive model by adding the features of 1 positive core and volume ≧45 cm3 to d’Amico’s criteria. This allows to preoperatively distinguish between patients that most probably would benefit from radical treatment and patients that might be offered active surveillance.
Long-Term Outcome of Patients with High-Risk Prostate Cancer following Radical Prostatectomy and Stage-Dependent Adjuvant Androgen Deprivation
Authors: Spahn Martin , Weiss Christel , Bader Pia , Ströbel Philipp , Gerharz Elmar W. , Kneitz Burkard , Frohneberg Detlef
Published: March 2010

Purpose: To present the long-term outcome of high-risk prostate cancer patients treated by radical retropubic prostatectomy (RRP) and stage-dependent adjuvant androgen deprivation therapy. Patients and Methods: Between 1989 and 2005, 2,655 patients underwent RRP by 9 surgeons. All cases (n = 372) with high-risk prostate cancer (serum PSA >20 ng/ml, and/or clinical stage T2c or greater, and/or biopsy Gleason score 8 or greater) were identified and analyzed retrospectively. Results: At 5 and 10 years, cancer-specific survival was 91.3 and 87.2%; overall survival was 84.3 and 72.1%; biochemical progression-free survival (BPFS) was 76.6 and 56.2%; clinical progression-free survival was 86.2 and 79.9%. Kaplan-Meier analysis showed significant differences with respect to pathological stage and Gleason score for cancer-specific survival, BPFS and clinical progression-free survival. In multiple analysis, the only preoperative predictor of BPFS at the 5% level was clinical stage (p = 0.0055). Conclusion: In patients with high-risk prostate cancer and a life expectancy of more than 10 years, RRP with stage-dependent adjuvant androgen deprivation therapy is a viable alternative to radiation therapy.
External Validation of the 2007 and 2001 Partin Tables in Irish Prostate Cancer Patients
Authors: Fanning D.M. , Fan Y. , Fitzpatrick J.M. , Watson R.W.G.
Published: March 2010

Introduction: External validation of predictive prostate cancer nomograms is of critical importance within distinct geographical locations, prior to their institution into routine clinical practice. We performed external validation of the 2007 and 2001 Partin tables in a cohort of Irish prostate cancer patients. Patients and Methods: Men enrolled in the Irish Prostate Cancer Research Consortium (n = 175) and who had undergone radical prostatectomy between 2004 and 2008 were used to externally validate the 2007 and 2001 Partin tables. A comparative analysis of the clinical and pathological parameters of the Irish and Partin patient cohorts was performed. The reported receiver operating characteristic (ROC) curve derived area under the curve (AUC) values were used to assess for variations in predictive accuracy. Statistical analyses were calculated with R software. Results: AUC values assigned to the differentiation of extra-prostatic extension and seminal vesicle invasion using the 2007 tables are 22 and 3%, respectively. The 2007 Partin tables showed superior accuracy for all parameters, excluding seminal vesicle invasion. Conclusion: Cumulatively the Partin tables showed poor discriminate ability for prediction of post-radical prostatectomy pathological outcomes in Irish men, necessitating caution in their clinical utilisation.
Incidence and Variables Predicting Gleason Score Up-Grading between Trans-Rectal Ultrasound-Guided Prostate Biopsies and Radical Prostatectomy
Authors: Bright Elizabeth , Manuel Clare , Goddard Jonathan C. , Khan Masood A.
Published: March 2010

Objective: To determine whether Gleason score up-grading is still occurring in men diagnosed with adenocarcinoma of the prostate via extended biopsy regimens, and factors that might predict this. Patients and Methods: Between September 1999 and February 2007, 211 men (age: 42–70 years; mean: 60 years) underwent trans-rectal ultrasound-guided prostate biopsies confirming clinically localized adenocarcinoma followed by radical prostatectomy (RP), within our department. Univariate and multivariate logistic regression (LR) analyses using age, serum PSA, prostate volume, clinical stage and total length of cores taken were performed to determine whether Gleason score up-grading could be predicted. Results: A total of 7/20 (35%), 24/64 (38%) and 36/127 (28%) men with 6, 7–9 and at least 10 core biopsies experienced Gleason score up-grading (p = nonsignificant between the 3 groups). Both univariate and multivariate LR analyses failed to determine any of our variables as a predictor of Gleason score up-grading from biopsy to RP. Conclusion: Despite increasing the number of cores taken at biopsy, in order to improve prostate cancer diagnosis, a substantial percentage of men still experience Gleason score up-grading from biopsy to RP. In addition, we were unable to determine any predicting factors for this up-grading.
Impacts of Antibiotic and Anti-Inflammatory Therapies on Serum Prostate-Specific Antigen Levels in the Presence of Prostatic Inflammation: A Prospective Randomized Controlled Trial
Authors: Ugurlu Ozgur , Yaris Mehmet , Oztekin C. Volkan , Kosan T. Murat , Adsan Oztug , Cetinkaya Mesut
Published: March 2010

Introduction: The aim of this study was to determine if antibiotic or anti-inflammatory medications lower serum prostate-specific antigen (PSA) in the presence or absence of inflammation in the prostatic secretions of patients with PSA levels between 2.5 and 10 ng/ml and normal digital rectal examinations (DRE). Materials and Methods: Patients with PSA levels between 2.5 and 10 ng/ml and normal DRE were candidates for the study. One hundred and eight patients with positive expressed prostate secretion (EPS) were randomized into antibiotics, anti-inflammatory and control groups (groups 1, 2 and 3, respectively), and 108 patients with negative EPS were randomized into similar groups (groups 4, 5 and 6, respectively). Repeat PSA levels of all patients were obtained 6 weeks after randomization and 10 core prostate biopsies were performed. Results: Median PSA levels in group 1 before and after treatment were 5.2 (4.3–6.4) and 4.0 ng/ml (3.1–4.9), respectively (p < 0.001). The only significant decrease in PSA was observed in group 1. The percent change in PSA levels in group 1 was significantly greater than both in its control group (group 3; p < 0.001) and the EPS– antibiotics group (group 4; p < 0.001). Conclusions: Antibiotherapy significantly reduces serum PSA only in EPS+ patients, which justifies limiting the use of prebiopsy antibiotics to EPS+ patients with a normal DRE and PSA level between 2.5 and 10 ng/ml, minimizing the major drawbacks of empirical antibiotics usage.
Effect of Transurethral Resection of Prostate on Prostatic Resistive Index
Authors: Ozden Cuneyt , Gunay Isa , Deren Tagmac , Bulut Suleyman , Ozdal Ozdem Levent , Koparal Suha , Memis Ali
Published: March 2010

Introduction: In the present study, we evaluated the effect of transurethral resection of the prostate (TUR-P) on prostatic resistive index (RI) in patients with benign prostatic hyperplasia(BPH). Patients and Methods: Forty BPH patients who were candidates for prostatectomy were prospectively included in the study. Prostatic RI was measured using power Doppler imaging (PDI) before TUR-P. In the postoperative follow-up, all patients were reevaluated with PDI, International Prostate Symptom Score (IPSS) and uroflowmetry. Results: Mean age, IPSS and maximal urine flow rate (Qmax) of the patients was 65.8 ± 7.6 years, 24.6 ± 7.1 and 7.7 ± 3.8 ml/s, respectively. The mean prostatic RI of the patients before TUR-P was 0.79 ± 0.02. Prostatic RI positively correlated with total prostate volume and IPSS (r = 0.57, p = 0.0001, and r = 0.42, p = 0.008, respectively) and negatively correlated with Qmax (r = –0.37, p = 0.029) prior to treatment. After TUR-P, mean IPSS and prostatic RI significantly decreased (6.5 ± 4.3 and 0.68 ± 0.03, respectively; p < 0.05), whereas mean Qmax was increased (15.7 ± 5.7, p < 0.05). Conclusions: Our data demonstrated that prostatic RI of the patients with BPH significantly decreased after TUR-P. We believe that prostatic RI could be a useful parameter for the follow-up of patients who underwent TUR-P.
Importance of Axial Penile Rigidity in Objective Evaluation of Erection Quality in Patients with Erectile Dysfunction – Comparison with Radial Rigidity
Authors: Mizuno Ichiro , Komiya Akira , Watanabe Akihiko , Fuse Hideki
Published: March 2010

Introduction: The aim of this prospective study was to evaluate the usefulness of measurement of axial penile rigidity, compared with radial penile rigidity. Patients and Methods: Twenty-two patients, aged 21–75 years old (a mean of 50), with erectile dysfunction underwent axial penile rigidity measurements by the digital inflection rigidometer (DIR) as well as radial penile rigidity measurements by the RigiScan Plus during intracavernous pharmacological erection testing. Results: A significant correlation was recognized between axial rigidity, and radial rigidity at the tip (p = 0.0024) and base (p = 0.0098) of the penis. In 10 patients, the DIR revealed axial rigidity of 550 g or more, and they also had radial rigidity of 60% or more at the tip and base. In 14 and 17 subjects, radial rigidity of 60% or more was observed at the tip and base, respectively. Four of the former 14 and 7 of the latter 17 had axial rigidity <550 g. Conclusions: A RigiScan results of radial rigidity of 60% or more should be interpreted cautiously and not necessarily regarded as normal.
Pim1 Regulates Androgen-Dependent Survival Signaling in Prostate Cancer Cells
Authors: van der Poel H.G. , Zevenhoven J. , Bergman A.M.
Published: March 2010

Introduction: Pim1 overexpression was found to be associated with more advanced prostate cancer. Interleukin-6 (IL-6) induces Pim1 expression and is often found elevated after androgen-ablative therapy. Methods: Tumor tissue from 31 selected prostate cancer patients and cell lines were studied immunohistochemically for c-myc, Pim1, STAT3, pSTAT3-Tyr705, and androgen receptor (AR) expression. The effect of Pim1 on androgen dependence in prostate cancer was studied in transgene cell lines. Results: Pim1 expression was increased in high-grade prostate tumors (Gleason >7), irrespective of androgen status, was highest in hormone refractory prostate cancer and correlated to pSTAT3-Tyr705 expression levels. Co-expression of Pim1 and MYC was observed specifically after androgen ablation. Pim1 expression could be induced in LNCaP and PC3 cells by IL-6. Pim1 overexpression in PC3 and PNCaP increased the transcriptional activity of the AR at low levels of dihydrotestosterone. Consequently, Pim1 expression increased LNCaP cell survival specifically at castrate levels of androgen. Conclusions: Pim1 expression was increased in primary tumor samples after androgen ablation. Pim1 overexpression increased AR transcriptional activity in a ligand-dependent manner in prostate cancer cell lines, resulting in enhanced cell survival at castrate levels of androgen.
Expression Changes of Transforming Growth Factor-Beta1 and Thrombospondin-1 in Cavernous Tissues of Diabetic Rats
Authors: Zhang Xiao-Ming , Shi Pei-Hua , Cao Sai-Hong , Yu He-Jun , Azad Junaid , Ling Shu-Cai
Published: March 2010

Objective: To assess transforming growth factor-β1 (TGF-β1) and thrombospondin-1 (TSP-1) expression in the cavernous tissue of rats with streptozotocin (STZ)-induced diabetes. Materials and Methods: Twenty male Sprague-Dawley rats were randomly divided into 2 groups: diabetics and controls. We injected STZ intraperitoneally to induce diabetes, and studied the alterations in TGF-β1 and TSP-1 expression in the cavernous tissue of the 2 groups by immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction. HE staining was also applied to determine morphological changes. Weight, blood sugar and urine sugar were measured before and after model induction in both groups. Results: Expression of TGF-β1 and TSP-1 increased significantly in the cavernous tissue of the diabetic rats compared to the control group. Conclusions: TGF-β1 and TSP-1 expression changes in cavernous tissues may play an important role in diabetic erectile dysfunction.
Varicocele: in Search of a Human Model
Authors: Das Adhikary Samiran , Gopalakrishnan Ganesh
Published: March 2010

Aims: To study the effects of left gonadal vein ligation on semen parameters and venous hemodynamics of the testis. Subjects and Methods: All male voluntary kidney donors who were scheduled to have left donor nephrectomy between March 2004 and February 2005, by either open or laparoscopic technique, were considered for this study. Results: A total of 95 live related renal transplants were performed. Left donor nephrectomy was performed in 22 of 37 males. Only 19 were evaluable; 7 patients underwent laparoscopic donor nephrectomy; 6 were unmarried. We observed that 66% (12) of our study patients showed radiological evidence of varicocele, and this was statistically significant; 22% (4) also developed contralateral varicocele; 44% (8) developed oligoasthenozoospermia. Conclusion: Ligation of the left gonadal vein is part of organ harvesting for live related renal transplantation and produces radiologically confirmed varicocele in some men. In these men, alterations in semen parameters are observed over 4–24 weeks. Due to short follow-up, we are unable to state if this is a permanent or temporary effect. We presume that since these men had normal semen parameters earlier, the stress pattern would revert to normal. If it does not however, this would have particular implications upon informed consent for unmarried male donors.
Relaxation Effect of Phosphodiesterase-5 Inhibitor on the Animal Bladder and Prostatic Urethra: in vitro and in vivo Study
Authors: Lee Jeong Gu , Moon Du Geon , Kang Seok Ho , Cho Dae Yeon , Park Hong Seok , Bae Jae Hyun
Published: March 2010

Aim: To assess the relaxation effect of the phosphodiesterase-5 inhibitor udenafil on the bladder and prostatic urethra and its therapeutic potentials for benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). Methods: For the in vitro study, muscle strips from urinary bladder and urethra were prepared from male New Zealand rabbits. The strips were mounted in organ baths and connected to force transducers. After stabilization, maximal tissue contractions were obtained by the addition of phenylepinephrine for urethra strips and carbachol for bladder strips. When the contraction was stabilized, a dose-response curve of udenafil was constructed. For the in vivo study using adult male Sprague-Dawley rats, changes of intravesical pressure and urethral perfusion pressure after intraarterial administration of udenafil were monitored. Results: Udenafil significantly relaxed the bladder and urethra strips in a dose-dependent manner. At 10–3 M, udenafil induced a significant relaxation of the bladder strips by 37.3% and of the urethra strips by 44.0%. In the in vivo study, the intercontraction interval was significantly prolonged (p < 0.01) and the duration of urethral relaxation with high-frequency oscillations was significantly prolonged (p < 0.01) after udenafil. Conclusions: Udenafil had relaxant effects on the bladder and prostatic urethral smooth muscle. Clinically, udenafil could be applied as an effective treatment for BPH/LUTS.
Chronic Subdural Hematoma Associated with Voiding Dysfunction
Authors: Abdel Hafez A.A.R. , Badawi A.A. , Rohrmann D. , Jakse G.
Published: March 2010

We report the case of a 73-year-old male who presented with a chronic subdural hematoma that compressed the frontal lobe, an area known to be active in detrusor control, and caused contralateral hemiparesis and urgency incontinence. Urodynamically, he had a small bladder capacity and high amplitude overactive detrusor contractions with an intact sphincteric response. We concluded that the effect of intracranial lesions on voiding depends upon the site rather than the type of the pathology. Further in-depth studies are needed to clarify the effect of intracranial lesions, and accordingly the function of different brain regions and their influence on voiding.
Laparoscopic Pyelovesicostomy for Giant Hydronephrosis in a Solitary Kidney
Authors: Pal Bipin Chandra , Shah Shailesh A. , Gupta Sandeep , Trivedi Pankaj
Published: March 2010

Pyelovesicostomy has rarely been described in the literature. Most of the time this procedure has been performed in cases of ureteral obstruction in an ectopic kidney or in a transplanted kidney. We report the case of a 16-year-old male who presented with a history of large abdominal swelling and pain. On investigation he was found to have a solitary right kidney with giant hydronephrosis and to be in renal failure. An initial percutaneous nephrolithotomy diversion was performed followed 1 month later by right laparoscopic pyelovesicostomy. The postoperative period was uneventful. We describe laparoscopic pyelovesicostomy in the management of giant hydronephrosis for the first time. Our case illustrates that laparoscopic pyelovesicostomy is a feasible option in the management of giant hydronephrosis.
Link between Interleukin-10 Level and Outcome after Ischemic Stroke
Authors: Chang Li-Teh , Yuen Chun-Man , Liou Chia-Wei , Lu Cheng-Hsien , Chang Wen-Neng , Youssef Ali A. , Yip Hon-Kan
Published: March 2010

Objectives: The prognostic value of interleukin (IL)-10 in patients after acute ischemic stroke (IS) is not well understood. This study tested the hypothesis that serum levels of IL-10 are substantially increased after IS and predictive of IS outcome. Methods: Serum IL-10 levels were examined 48 h after acute IS in 135 consecutive patients, and in 20 healthy and 30 at-risk controls. Results: Mean serum IL-10 was significantly higher in IS patients than in both control groups (p < 0.0001, respectively). Additionally, serum IL-10 was significantly higher in patients with severe neurological impairment [defined as a score ≧12 on the National Institute of Health Stroke Scale (NIHSS)] than in patients with less severe neurological impairment (NIHSS score <12) 48 h after IS (p < 0.0001). Furthermore, higher serum IL-10 was strongly and independently correlated with severe neurological impairment (NIHSS ≧12) 48 h after acute IS (p < 0.0001), and independently predictive of combined major adverse clinical outcomes (defined as recurrent IS, any cause of death or NIHSS ≧12) on day 90 following IS (p < 0.0001). Conclusions: Serum IL-10 is an independent prognosticator of IS outcome.
The Effect of Early-Life Stress on Airway Inflammation in Adult Mice
Authors: Vig Rattanjeet , Gordon John R. , Thébaud Bernard , Befus A. Dean , Vliagoftis Harissios
Published: March 2010

Background/Aims: Neonatal stress induces permanent physiological changes that may influence the immune system. Early-life stress increases asthma disease severity in children. We investigated the effects of early-life stress on allergic airway inflammation using a murine model of asthma coupled to maternal separation as an early-life stress stimulus. Methods: Maternally separated (MS) and unseparated control (CON) mice were sensitized with ovalbumin (OVA) beginning at day 31 after birth. Results: Challenging mice with OVA increased airway hyperresponsiveness (AHR) and the number of inflammatory cells recovered in the bronchoalveolar lavage (BAL), compared to saline-challenged mice. Challenging MS mice with OVA resulted in less total inflammatory cells, eosinophils, interferon-γ, and interleukin-4 in BAL compared to CON mice. However, MS mice challenged with OVA exhibited AHR similar to CON mice challenged with OVA. In contrast, an enhanced stress protocol (MS+) involving removal of pups from their home cages following the removal of the dam resulted in inflammatory cell accumulation and cytokine levels in the BAL similar to CON mice and higher than MS mice. Conclusions: These findings indicate that the effect of early-life psychological factors on the development of airway inflammatory diseases such as asthma is very complex and depends on the quality of the psychological stress stimulus.
Chronic Individual Housing-Induced Stress Decreased Expression of Catecholamine Biosynthetic Enzyme Genes and Proteins in Spleen of Adult Rats
Authors: Gavrilovic Ljubica , Spasojevic Natasa , Dronjak Sladjana
Published: March 2010

Objective: Social isolation is regarded as one of the most relevant causes of diseases in mammalian species. The activation of the sympathoneural system represents one of the key components of the stress response. The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions. The aim of the present study was to determine plasma epinephrine and norepinephrine in individually housed rats, as well as to find out whether splenic gene expression of catecholamine synthesizing enzymes and their protein levels are affected by chronic psychosocial stress. Methods: Tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels were quantified by quantitative real-time RT-PCR. The TH, DBH and PNMT immunoproteins were assayed by Western blot. Results: Chronic social isolation of adult male rats produced a significant increase in plasma catecholamine levels and a decrease in splenic TH mRNA, DBH mRNA and PNMT mRNA. Protein levels of TH, DBH and PNMT were also reduced. Conclusion: These results suggest that increased plasma catecholamines and decreased gene expression and protein levels of catecholamine biosynthetic enzymes in the spleen of chronically individually housed animals might reduce catecholamine synthesis, thus leaving the immunocompetent tissues depleted of catecholamines and consequently leading to an impairment of immune response.
Passive Immunization with LINGO-1 Polyclonal Antiserum Afforded Neuroprotection and Promoted Functional Recovery in a Rat Model of Spinal Cord Injury
Authors: Lv Jun , Xu Ru-xiang , Jiang Xiao-dan , Lu Xin , Ke Yi-quan , Cai Ying-qian , Du Mou-xuan , Hu Changchen , Zou Yu-xi , Qin Ling-sha , Zeng Yan-jun
Published: March 2010

LINGO-1 (leucine-rich repeat and Ig domain-containing, Nogo receptor-interacting protein) is an important component of the NgR receptor complex involved in RhoA activation and axon regeneration. The authors report on passive immunization with LINGO-1 polyclonal antiserum, a therapeutic approach to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). The intrathecally administered high-titer rabbit-derived antiserum can be detected around the injury site within a wide time window; it blocks LINGO-1 in vivo with high molecular specificity. In this animal model, passive immunization with LINGO-1 antiserum significantly decreased RhoA activation and increased neuronal survival. Adult rats immunized in this manner show recovery of certain hindlimb motor functions after dorsal hemisection of the spinal cord. Thus, passive immunotherapy with LINGO-1 polyclonal antiserum may represent a promising repair strategy following acute SCI.
Exhaustive Exercise Reduces Tumor Necrosis Factor-α Production in Response to Lipopolysaccharide in Mice
Authors: Tanaka Yohei , Kawanishi Noriaki , Shiva Daisuke , Tsutsumi Noritsugu , Uchida Masataka , Kitamura Hiromi , Kato Yasuko , Yano Hiromi
Published: March 2010

Objective: Stressful exercise reduces the plasma pro-inflammatory cytokine concentration in response to lipopolysaccharide (LPS). The aim of this study was to clarify the mechanism of exhaustive exercise-induced suppression of the plasma tumor necrosis factor (TNF)-α concentration in response to LPS. Methods: Male C3H/HeN mice (n = 66) were randomized to treadmill running to exhaustion (Ex) or a sedentary (Non-Ex) condition. Monocytes and splenic macrophages were collected from some animals, and other animals were injected with LPS (1 mg/kg) immediately after the exercise. The liver, lung and spleen tissues in the mice were removed 30 min after the LPS injection for determination of TNF-α mRNA expression. Blood and tissue samples were collected for determination of TNF-α and TNF receptors (TNFR) 1 h after the LPS injection. Results: Although there was a significant suppression in LPS-induced plasma TNF-α in the Ex mice when compared to the Non-Ex mice (p < 0.01), soluble TNFR in plasma was not affected by the exercise. There was no change in cell-surface expression of Toll-like receptor 4 (TLR4) and in LPS-induced TNF-α mRNA expression and TNFR content in tissues between the Ex and Non-Ex groups. Interestingly, TNF-α contents in the liver, lung and spleen of the Ex mice were significantly lower than those of the Non-Ex group (p < 0.01, p < 0.01 and p < 0.05, respectively). Conclusion: These data suggest that exhaustive exercise-induced suppression of the plasma TNF-α concentration despite LPS stimulation might depend on translation of TNF-α in tissues.
Improved Lipid and Glucose Metabolism in Transgenic Rats With Increased Circulating Angiotensin-(1-7)
Authors: Santos Sérgio Henrique S. , Braga Janaina Felix , Mario Érica Guilhen , Pôrto Laura Cristina J. , Rodrigues-Machado Maria da Glória , Murari Antonela , Botion Leida Maria , Alenina Natalia , Bader Michael , Santos Robson Augusto S.
Published: March 2010

Objective—

Obesity and diabetes remain among the world’s most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR).

Methods and Results—

The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR.

Conclusion—

These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism.
Simvastatin Decreases Endothelial Progenitor Cell Apoptosis in the Kidney of Hypertensive Hypercholesterolemic Pigs
Authors: Lavi Ronit , Zhu Xiang-Yang , Chade Alejandro R. , Lin Jing , Lerman Amir , Lerman Lilach O.
Published: March 2010

Objective—

Hypertension and hypercholesterolemia might interfere with renal repair mechanisms. We hypothesized that simvastatin improves the survival of endothelial progenitor cells (EPC) in the renal microenvironment imposed by concurrent renovascular hypertension and dietary hypercholesterolemia (HTC).

Methods and Results—

Pigs were studied after 12 weeks of no intervention (n=6), HTC (n=6), or HTC+ oral simvastatin supplementation (80 mg/day, n=5). EPC were also isolated and studied in vitro after exposure to the proapoptotic oxidized low-density lipoprotein with or without coincubation with simvastatin. Renal hemodynamics, function, and endothelial function were evaluated in vivo, and the number of CD34+/KDR+ EPC, apoptosis, oxidative stress, inflammation, and fibrosis in renal tissue studied ex vivo. Compared with normal kidney, the HTC kidney showed endothelial dysfunction and increased oxidative stress, interstitial macrophage filtration, and fibrosis. The number of EPC in the kidney increased, as did their apoptosis (0.85±0.24% versus 0.22±0.07%,
P
<0.05 versus normal). Simvastatin did not affect blood pressure, cholesterol levels, basal renal function, or number of renal EPC in HTC, but it improved endothelial function; blunted renal oxidative stress, inflammation, and fibrosis; and attenuated EPC apoptosis (to 0.37±0.09%,
P
<0.05 versus HTC). Simvastatin also significantly decreased oxidized low-density lipoprotein–induced EPC apoptosis in vitro.

Conclusion—

EPC are recruited but undergo apoptosis in the HTC kidney, likely because of a hostile microenvironment. Simvastatin rescues renal repair mechanisms in HTC and counteracts renal damage, which may account for its protective effects on the kidney during exposure to cardiovascular risk factors.
Pim-1 Kinase Protects Mitochondrial Integrity in Cardiomyocytes
Authors: Borillo Gwynngelle A. , Mason Matt , Quijada Pearl , Völkers Mirko , Cottage Christopher , McGregor Michael , Din Shabana , Fischer Kimberlee , Gude Natalie , Avitabile Daniele , Barlow Steven , Alvarez Roberto , Truffa Silvia , Whittaker Ross , Glassy Matthew S. , Gustafsson Asa B. , Miyamoto Shigeki , Glembotski Christopher C. , Gottlieb Roberta A. , Brown Joan Heller , Sussman Mark A.
Published: March 2010

Rationale
:

Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details antiapoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity.

Objective
:

The purpose of this study is to demonstrate that the cardioprotective kinase Pim-1 acts to inhibit cell death by preserving mitochondrial integrity in cardiomyocytes.

Methods and Results
:

A combination of biochemical, molecular, and microscopic analyses demonstrate beneficial effects of Pim-1 on mitochondrial integrity. Pim-1 protein level increases in the mitochondrial fraction with a corresponding decrease in the cytosolic fraction of myocardial lysates from hearts subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Cardiac-specific overexpression of Pim-1 results in higher levels of antiapoptotic Bcl-X
L
and Bcl-2 compared to samples from normal hearts. In response to oxidative stress challenge, Pim-1 preserves the inner mitochondrial membrane potential. Ultrastructure of the mitochondria is maintained by Pim-1 activity, which prevents swelling induced by calcium overload. Finally, mitochondria isolated from hearts created with cardiac-specific overexpression of Pim-1 show inhibition of cytochrome
c
release triggered by a truncated form of proapoptotic Bid.

Conclusion
:

Cardioprotective action of Pim-1 kinase includes preservation of mitochondrial integrity during cardiomyopathic challenge conditions, thereby raising the potential for Pim-1 kinase activation as a therapeutic interventional approach to inhibit cell death by antagonizing proapoptotic Bcl-2 family members that regulate the intrinsic apoptotic pathway.
Platelets Play an Essential Role in Separating the Blood and Lymphatic Vasculatures During Embryonic Angiogenesis
Authors: Carramolino Laura , Fuentes Joana , García-Andrés Clara , Azcoitia Valeria , Riethmacher Dieter , Torres Miguel
Published: March 2010

Rationale
:

Several mutations that impair the development of blood lineages in the mouse also impair the formation of the lymphatic vasculature and its separation from the blood vasculature. However, the basis for these defects has remained unknown because the mutations characterized affect more than one blood lineage.

Objective
:

We tested the hypothesis that megakaryocytes/platelets are required for the formation of the lymphatic vasculature and its separation from the blood vascular system.

Methods and Results
:

We characterized the vascular patterning defects of mice deficient for the homeodomain transcription factor
Meis1
(myeloid ecotropic viral integration site 1), which completely lack megakaryocyte/platelets.
Meis1
null embryos fail to separate the blood and lymphatic vasculature, showing blood-filled primary lymphatic sacs and superficial lymphatic vessels. To test the involvement of megakaryocytes/platelets in this phenotype, we generated megakaryocyte/platelet-specific deficient mice by targeted lineage ablation, without affecting other blood lineages. This model reproduces the lymphatic/blood vasculature separation defects observed in
Meis1
mutants. A similar phenotype was induced by antibody-mediated ablation of circulating platelets in wild type mice. Strong association of platelets with vascular endothelium at regions of contact between lymphatic sacs and veins confirmed a direct role of platelets in the separation of the 2 vasculatures.

Conclusions
:

In addition to their known protective function in the response accidental vascular injury, platelets are also required during embryonic lymphangiogenesis for the separation of the nascent lymphatic vasculature from blood vessels.
Hepatocyte Growth Factor and the Risk of Ischemic Stroke Developing Among Postmenopausal Women
Authors: Rajpathak Swapnil N. , Wang Tao , Wassertheil-Smoller Sylvia , Strickler Howard D. , Kaplan Robert C. , McGinn Aileen P. , Wildman Rachel P. , Rosenbaum Daniel , Rohan Thomas E. , Scherer Philipp E. , Cushman Mary , Ho Gloria Y.F.
Published: March 2010

Background and Purpose—

Hepatocyte growth factor (HGF) is a potent angiogenic factor and may play a role in the development and progression of atherosclerotic lesions, the underlying mechanism of cardiovascular disease. However, there have been no prospective studies examining the relationship between HGF levels and risk of stroke.

Methods—

We conducted a nested case-control study (972 incident stroke cases and 1:1 age-matched and race-matched controls) to prospectively evaluate the association between plasma HGF and risk of ischemic stroke within the Women’s Health Initiative Observational Study, a cohort of postmenopausal women aged 50 to 79 years.

Results—

Baseline HGF levels were correlated positively with body mass index, systolic blood pressure, low-density lipoprotein cholesterol, insulin resistance, and inflammatory markers, such as C-reactive protein, and inversely with high-density lipoprotein cholesterol (all
P
<0.05). Baseline HGF levels were higher among cases than controls (geometric means, 601.8 vs 523.2 pg/mL;
P
=0.003). Furthermore, the risk of incident ischemic stroke was significantly greater among women in the highest vs lowest quartile of plasma HGF levels (OR, 1.46; 95% CI, 1.12–1.91;
P
trend
=0.003) in a conditional logistic regression model that adjusted for body mass index. These results were only slightly attenuated after further adjustment for additional stroke risk factors (OR, 1.39; 95% CI, 1.04–1.85;
P
trend
=0.023).

Conclusions—

Circulating levels of HGF are associated with an increased risk of incident ischemic stroke, independent of obesity and other risk factors for cardiovascular disease, among postmenopausal women aged 50 to 79 years.
The Beta-hCG+Erythropoietin in Acute Stroke (BETAS) Study
Authors: Cramer Steven C. , Fitzpatrick Camille , Warren Michael , Hill Michael D. , Brown David , Whitaker Laura , Ryckborst Karla J. , Plon Lawrence
Published: March 2010

Background and Purpose—

Animal data suggest the use of β-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial.

Methods—

Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of β-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific end points.

Results—

A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for deep vein thrombosis and serial measures of serum hemoglobin. In several instances, domain-specific end points provided greater insight into impairments as compared with global outcome measures.

Conclusions—

Results support the safety of this sequential, 2-growth factor therapy initiated 24 to 48 hours after stroke onset.
Medical Complications Among Hospitalizations for Ischemic Stroke in the United States From 1998 to 2007
Authors: Tong Xin , Kuklina Elena V. , Gillespie Cathleen , George Mary G.
Published: March 2010

Background and Purpose—

The common medical complications after ischemic stroke are associated with increased mortality and resource use.

Method—

The study population consisted of 1 150 336 adult hospitalizations with ischemic stroke as a primary diagnosis included in the 1998 to 2007 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Multiple logistic regression analyses were used to examine changes between 1998 to 1999 and 2006 to 2007 in the prevalence of acute myocardial infarction, pneumonia, deep venous thrombosis, pulmonary embolism, or urinary tract infection, in-hospital mortality, and length of stay.

Results—

In 2006 to 2007, the prevalence of hospitalizations with a secondary diagnosis of acute myocardial infarction, pneumonia, deep venous thrombosis, pulmonary embolism, and urinary tract infection was 1.6%, 2.9%, 0.8%, 0.3%, and 10.1%, respectively. The adjusted ORs for a hospitalization in 2006 to 2007 complicated by acute myocardial infarction, deep venous thrombosis, pulmonary embolism, or urinary tract infection, using 1998 to 1999 as the referent, were 1.39, 1.68, 2.39, and 1.18, respectively. The odds of pneumonia did not change significantly between 1998 to 1999 and 2006 to 2007. In-hospital mortality was significantly lower in 2006 to 2007 than in 1998 to 1999. Despite the overall length of stay decreasing significantly from 1998 to 1999 to 2006 to 2007, it remained the same for hospitalizations with acute myocardial infarction, pneumonia, deep vein thrombosis, and pulmonary embolism.

Conclusion—

Although in-hospital mortality decreased over the study period, 4 of the 5 complications were more common in 2006 to 2007 than they were 8 years earlier with the largest increase observed for deep venous thrombosis and pulmonary embolism.
The Gospel of Thomas (Pynchon): Abandoning Eschatology in Gravity’s Rainbow
Authors: Pederson Joshua
Published: March 2010

It is tempting to read Thomas Pynchon’s sprawling masterpiece Gravity’s Rainbow—with its shell-shocked refugees fleeing across a missile-pocked, post-war landscape—as an eschatological text that plays out religious end-times scenarios. However, an invented citation from the non-canonical Gospel of Thomas included as a chapter epigraph—“Dear Mom, I put a couple of people in hell today”—suggests that we should do otherwise. In grafting a playful fragment about Jesus, judgment, and hell onto Thomas, Pynchon parodies a common need to read eschatological themes back into non-eschatological texts. In doing so, he also provides a powerful heuristic for interpreting his own book. Ultimately, Pynchon’s own rocket-gospel is likewise a non-eschatological text. Like Thomas, Gravity’s Rainbow stymies readers’ efforts to derive a clear eschatology from it—or to read one back into it. In this essay, I contend that Pynchon enacts a number of strategies to keep his audience from reading classic end-times scenarios into his own work, all of which are prefigured by the Gospel of Thomas.
Cessation of the 22–25 June 2006 Coastally Trapped Wind Reversal
Authors: Rahn David A. , Parish Thomas R.
Published: March 2010

Coastally trapped wind reversals (CTWRs) occur periodically in the marine boundary layer off the western coast of the United States and dramatically change the low-level wind regime and coastal weather. Southerly flow becomes established with the passage of a CTWR along with cooler temperatures and a low stratus deck in a narrow band along the coast. CTWRs can propagate northward along the coast for hundreds of kilometers. A strong CTWR commenced in southern California on 22 June 2006 and moved north along the California coastline before stalling at Cape Mendocino on 24 June 2006. A transcritical Froude number differentiates the CTWR layer from the climatologically favored northern wind regime to the north of Cape Mendocino and indicates a barrier to the movement of a density current. A well-defined cloud boundary is present as detected by radar and satellite imagery and sharp gradients exist in the basic-state parameters as measured by instrumented aircraft. As the Pacific high migrates back offshore, the horizontal pressure field near Cape Mendocino becomes increasingly adverse to the continued northward movement of the CTWR layer and typical summertime conditions are reestablished. Observations and modeling results show that the cessation phase of this CTWR was characterized by a surprising lack of topographic blocking due to the mountainous coastal terrain and Cape Mendocino massif. The horizontal pressure field over the ocean to the north of the CTWR was the key impeding force to continued propagation of this event.
Dynamical Feedbacks of the Southern Annular Mode in Winter and Summer
Authors: Barnes Elizabeth A. , Hartmann Dennis L.
Published: March 2010

The persistence of the southern annular mode (SAM) is studied during austral winter (June–September) and summer (December–March) using observations of the three-dimensional vorticity budget. Analysis of the relative vorticity tendency equation shows that convergence of eddy vorticity flux in the upper troposphere, coupled with a secondary circulation, constitutes a positive eddy feedback that acts to sustain the vorticity anomaly associated with the jet shift against drag. The feedback exhibits a strong seasonality, with summer months revealing a positive feedback through much of the hemisphere and winter months showing a positive feedback over the Indian Ocean but not over the western Pacific. Results suggest that the lack of wintertime feedback over the western Pacific is due to the weakness of the eddy-driven midlatitude jet in that region.