bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug resistance protein 4 mediates cAMP efflux from rat preglomerular vascular smooth muscle cells
Authors: Cheng Dongmei , Ren Jin , Jackson Edwin K 
Published: August 2009

Summary1. Previous studies have shown that stimulation of adenylyl cyclase in preglomerular vascular smooth muscle cells (PGVSMC) increases extracellular cAMP; however, the mechanism by which PGVSMC transport intracellular cAMP into the extracellular milieu is unknown.2. We hypothesize that multidrug resistance protein (MRP) 4 is the primary transporter mediating efflux of intracellular cAMP from PGVSMC.3. Both reverse transcription–polymerase chain reaction and real‐time polymerase chain reaction detected MRP4 mRNA in PGVSMC in culture. Moreover, western blotting using an antibody specific for MRP4 gave rise to a 150 kDa signal, consistent with the presence of MRP4 protein in PGVSMC.4. Specifically designed short interference (si) RNA reduced MRP4 mRNA expression by 71% (P = 0.0075) and MRP4 protein by 80% (P = 0.0004).5. Isoproterenol (1 μmol/L) increased intracellular cAMP, which resulted in efflux of cAMP into the medium. The siRNA knockdown of MRP4 significantly reduced basal extracellular cAMP and nearly abolished isoproterenol‐induced increases in extracellular cAMP (P = 0.0143, interaction between isoproterenol and MRP4 siRNA in two‐factor analysis of variance). In isoproterenol‐treated cells, MRP4 siRNA decreased the ratio of extracellular cAMP to intracellular cAMP by 72% (P = 0.0019).6. We conclude that MRP4 is the dominant cAMP transporter in PGVSMC.
Peripheral arterial disease is associated with coronary artery spasm as assessed by an intracoronary acetylcholine provocation test
Authors: Chen Kang‐Yin , Rha Seung‐Woon , Li Yong‐Jian , Poddar Kanhaiya L , Jin Zhe , Minami Yoshiyasu , Wang Lin , Li Guang‐Ping , Saito Shigeru , Park Jae‐Hyoung , Na Jin‐Oh , Choi Cheol Ung , Lim Hong‐Euy , Kim Jin‐Won , Kim Eung‐Ju , Park Chang‐Gyu , Seo Hong‐Seog , Oh Dong‐Joo 
Published: August 2009

Summary1. Both peripheral arterial disease (PAD) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS may be expected in patients with PAD. In the present study, we evaluated the incidence and characteristics of CAS in patients with PAD.2. A total of 78 patients with PAD and 241 age‐ and gender‐matched patients without PAD who had chest pain with normal coronary appearance on coronary angiograms underwent intracoronary acetylcholine (ACh) provocation test. Acetylcholine was injected into the left coronary artery in incremental doses of 20, 50 and 100 μg/min. Significant CAS was defined as a transient > 70% luminal narrowing with concurrent chest pain and/or ST segment changes.3. Patients with PAD had a significantly higher incidence of ACh‐induced significant CAS than those without PAD (60.3 vs 34.0%, respectively P < 0.001), as well as chest pain and ST segment changes during the ACh provocation test. Patients with PAD were more sensitive to lower doses of ACh and had a higher incidence of multivessel spasm than those without PAD. Multivariable logistic analysis showed that age, current smoking, PAD and myocardial bridge were independent predictors of ACh‐induced significant CAS. Moreover, of these factors, PAD was the strongest independent predictor (odds ratio 4.25; confidence interval 1.33–13.54; P = 0.014).4. In patients with chest pain, the presence of arterial disease at another site should still push the clinician towards treating the chest pain as angina, even if the coronary anatomy is normal on a coronary angiogram.
Peroxisome proliferator‐activated receptor‐γ coactivator‐1α in muscle links metabolism to inflammation
Authors: Handschin Christoph 
Published: August 2009

Summary1. In higher eukaryotes, metabolism and immunity are tightly coupled. However, whereas in evolutionary terms a compromised immune response due to undernourishment has been the predominant problem, the inflammatory response to obesity and other lifestyle‐associated diseases has increased in relevance in Western societies in the past 100 years.2. Traditionally, fat tissue has been considered as the major source of pro‐inflammatory secreted factors in these pathologies. However, in recent years the contribution of other tissues to disease‐causing chronic inflammation has been increasingly appreciated.3. Peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) is one of the key regulatory factors in active skeletal muscle. Aberrant expression of PGC‐1α in inactive muscle fibres could be linked to a sedentary lifestyle, persistent systemic inflammation and a higher risk for many chronic diseases. Accordingly, modulation of PGC‐1α activity in skeletal muscle may have a broad range of therapeutic effects. Here, recent advances in the understanding of the role of muscle PGC‐1α in health and disease are reviewed.
Radical prostatectomy for high‐risk prostate cancer: Biochemical outcome
Authors: Kawamorita Naoki , Saito Seiichi , Ishidoya Shigeto , Ito Akihiro , Saito Hideo , Kato Masanori , Arai Yoichi 
Published: August 2009

Objectives:  To determine the biochemical outcome following radical prostatectomy alone in patients with high‐risk prostate cancer.Methods:  Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre‐operative data, we stratified the patients into low, intermediate, and high‐risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate‐specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL.Results:  The PSA failure‐free survival rate for the high‐risk group (n = 46) was 64.5% after a median follow‐up period of 39 months. Among patients with high‐risk disease, none with pathologically organ‐confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure‐free rate in patients with non organ‐confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) ≥30 was a significant independent predictor of extra prostatic extension.Conclusions:  Radical prostatectomy is feasible in high‐risk prostate cancer patients, only if they have a pathologically organ‐confined disease.
An audit of genetic testing in diagnosis of inherited retinal disorders: a prerequisite for gene‐specific intervention
Authors: Pradhan Monika , Hayes Ian , Vincent Andrea 
Published: August 2009

AbstractBackground:  There has been an exponential increase in the number of genes implicated in inherited retinal disease over the last decade, but the genetic and phenotypic heterogeneity limited mutation detection. The high cost of sequencing and long turn around times meant that gene testing was not a viable option, particularly in New Zealand. Recently, advancements including development of micro‐array‐based mutation analysis and non‐for‐profit laboratories have resulted in affordable and time‐efficient testing. This has enabled genetic diagnostics to become an integral component of the work‐up for inherited retinal disease.Methods:  Genetic testing for inherited retinal disorders was initiated via the Ocular Genetic Clinic in Auckland 2 years ago. A retrospective audit of genetic testing over this period was carried out. The results of these tests and outcomes are discussed.Results:  Thirty‐five probands have undergone genetic testing for retinal disorders. This has included X‐Linked Retinoschisis, Leber Congenital Amaurosis, Retinitis Pigmentosa, Albinism, Achromatopsia, Usher syndrome, Stargardt disease and Mitochondrial disease. Of these, 54% of tests (19/35) showed a rare variant or pathogenic mutation. Three couples have proceeded to investigate the options of prenatal diagnosis and/or pre‐implantation genetic diagnosis.Conclusion:  The introduction of genetic testing, largely via disease arrays, has been highly successful at clarifying disease genotype in our cohort. It is now a timely and cost‐effective investigation that should be elemental to the assessment of inherited retinal disease. Genetic testing in an opportune fashion permits genetic counselling, enables families to make reproductive choices and might allow the possibility of gene therapy interventions.
Relationship between myopia and allergen‐specific serum IgE levels in patients with allergic conjunctivitis
Authors: Mimura Tatsuya , Yamagami Satoru , Usui Tomohiko , Funatsu Hideharu , Noma Hidetaka , Honda Norihiko , Amano Shiro 
Published: August 2009

AbstractPurpose:  Various exogenous allergens can cause allergic conjunctivitis, whereas refractive errors are also related (as an endogenous factor) to the pathogenesis of allergic conjunctivitis. However, little is known about the interaction between exogenous and endogenous factors in patients with allergic conjunctivitis. We investigated the relationship between refractive errors and exogenous allergens in patients with allergic conjunctivitis.Methods:  Sixty patients with allergic conjunctivitis and 60 healthy subjects (non‐allergy patients) were enrolled. Refraction was carried out in all subjects. In addition, total immunoglobulin E (IgE) and specific IgE levels for 12 inhaled allergens were measured by the capsulated hydrolic carrier polymer system.Results:  The patients who were positive for‐specific IgE to indoor allergens had higher myopia than those who were negative, including those positive for house dust IgE (−3.66 ± 2.95 vs. −1.05 ± 3.39, P = 0.0015), Dermatophagoides pteronyssinus (D. pteronyssinus) IgE (−3.50 ± 2.91 vs. −1.01 ± 3.46, P = 0.0021), and acarus IgE (−3.45 ± 2.21 vs. −1.51 ± 3.73, P = 0.0087), whereas antibody‐positive and antibody‐negative patients for outdoor allergens showed no significant differences of refraction. Refractions in indoor group (−3.58 ± 3.42) and indoor/outdoor (−3.70 ± 2.64) group were higher than those in outdoor group (−0.84 ± 2.30, P = 0.0047 and P = 0.0032) and the non‐allergy group (−1.30 ± 1.48, P = 0.0082 and P = 0.0054) [‐refraction] was significantly correlated with total IgE (r = 0.333, P = 0.0093), house dust (r = 0.355, P = 0.0054) and D. pteronyssinus (r = 0.379, P = 0.0028), while no correlation between refractive error and outdoor allergens was proven.Conclusion:  These results suggest that specific IgE levels for indoor allergens, such as house dust, might be associated with refractive errors.
Rotation of the head might not be recommended for internal jugular puncture in infants and children
Authors: ARAI TOSHIMI , MATSUDA YOSHIFUMI , KOIZUKA KYOKO , YASUOKA ASAKO 
Published: August 2009

SummaryBackground:  Traditionally, we have been puncturing the internal jugular vein (IJV) with the head rotated. However, in adults it has been suggested that rotation of the head increases the magnitude of an overlapping of the IJV to the carotid artery (CA). Therefore, in infants and children, we have examined anatomic relationship between the IJV and the CA under the head in midline and head in rotated position.Method:  Eleven infants and 51 children were included. Under general anesthesia, the patient was positioned in the Trendelenburg position with a shoulder roll to allow extension of the neck. At first, the head was placed in the midline position. The ultrasound probe was placed perpendicular to the skin, and images of the right IJV and CA were collected at the level of the cricoid cartilage. Then, the head was rotated to the left at 45°. The images were collected in the same way. The position of the right IJV relative to the CA was defined as anterior (A), anterolateral (AL), or lateral (L).Results:  Rotation of the head increased the magnitude of an overlapping because of more changes from L → AL, L → A, or AL → A (P < 0.05, Wilcoxon t‐test).Conclusion:  We conclude that the rotation of the head increases the magnitude of an overlapping of the IJV to the CA in infants and children.
A prospective multicentre study to investigate percutaneous tibial nerve stimulation for the treatment of faecal incontinence
Authors: Govaert B. , Pares D. , Delgado‐Aros S. , La Torre F. , Van Gemert W. G. , Baeten C. G. 
Published: August 2009

AbstractAim  Percutaneous tibial nerve stimulation (PTNS) is a minimal invasive treatment that can be performed in the outpatient clinic. This is a pilot study to investigate PTNS in the treatment of faecal incontinence.Method  Percutaneous tibial nerve stimulation was performed by insertion of a needle electrode near the posterior tibial nerve. Patients were treated twice a week. Evaluation of faecal incontinence and quality of life was performed at baseline, 6 weeks, 3 months, 6 months and 1 year. Quality of life was estimated using SF‐36 and FIQL questionnaires.Results  A total of 22 patients were included. The mean age was 60.4 ± 11.7 years. After 6 weeks, 18 continued the treatment; 13 patients had a > 50% decrease in incontinence episodes. Overall incontinence episodes fell from 19.6 ± 21.0 at baseline to 9.9 ± 15.5 (P = 0.082) at 6 weeks and to 3.6 ± 4.8 (P = 0.029) at 1 year. Postponement time and quality of life increased significantly during follow up.Conclusion  Percutaneous tibial nerve stimulation is simple and can be used in the outpatient setting. Good results can be obtained and sustained during maintenance treatment.
Clinical features’ diagnostics and treatment of Hirschsprung’s disease in adults
Authors: Vorobyov G. I. , Achkasov S. I. , Biryukov O. M. 
Published: August 2009

AbstractAim  Hirschsprung’s disease first diagnosed in adulthood is symptomatic from early childhood in most cases. However, the condition is frequently masked when constipation is managed effectively by enemas and aperients. One third of the patients will experience progressive symptoms or complications, requiring urgent surgical intervention.Method  Ninety patients with adult Hirschsprung’s disease were observed by a combination of investigations: barium enema, anorectal physiology, estimation of acetylcholinesterase activity and a 60 mm full‐thickness strip biopsy. The latter two modalities were performed in selected patients where there was diagnostic uncertainty. Single‐staged resections, mostly modified Duhamel procedures, were performed in patients who were stable and fit, and with only a limited degree of megacolon present, and no other complications. Otherwise patients were temporarily defunctioned prior to staged resection. All patients underwent surgical treatment. Long‐term functional outcomes were expressed as good, satisfactory or poor.Results  Median age was 24.5 years, range 14–47 years, and 72.2% were men. Almost three quarters (73.3%) of the patients had symptoms dating from early childhood. Barium enema was diagnostic in 84.3%, and 36.2% had a positive, but weak rectoanal inhibitory reflex. Acetylcholinesterase staining was positive in 85.7%, but full‐thickness strip biopsy was positive in 100% of equivocal cases. A separate cadaveric study of unaffected individuals determined the true length of the normal physiological hypoganglionic zone, mean 24.4 mm and range 7.5–50 mm. Supra‐anal short segment Hirschprung’s disease was found in 5.6% patients, rectal involvement in 54.4%, rectosigmoid in 38.9% and total aganglionosis of the colon in 1.1%. Resection of the aganglionic zone and proximally dilated colon was performed as a single‐staged procedure in 67.8%. Staged surgery was carried out in 32.2%. A modified Duhamel procedure was performed in 91.2% of cases. A good or satisfactory functional outcome was achieved in 96.7%. Long‐term functional outcome after resection depends on the degree of preoperative megacolon present. Megacolon limited to the sigmoid colon was associated with a good outcome in 89.7%, but in only 66.7% with more proximal dilatation (P < 0.05).Conclusion  Occasionally, Hirschsprung’s disease presents in adulthood, with ongoing symptoms from early childhood or with the development of functional obstruction, faecal impaction and megacolon in later life. Diagnosis often requires multimodal investigation. A 60 mm full‐thickness strip biopsy confirms aganglionosis in 100%. A modified Duhamel procedure is the operation of choice.
Open muscle biopsy in suspected myopathy: diagnostic yield and clinical utility
Authors: Lai C.‐H. , Melli G. , Chang Y.‐J. , Skolasky R. L. , Corse A. M. , Wagner K. R. , Cornblath D. R. 
Published: August 2009

Background:  The purpose of the study was to investigate the diagnostic yield and clinical utility of open muscle biopsy and to identify pre‐biopsy factors that might predict useful clinical results for suspected myopathy.Methods:  Two‐hundred fifty‐eight muscle biopsies, performed for investigation of suspected myopathy, were evaluated.Results:  A specific clinical diagnosis following muscle biopsy was made in 43% of cases. As a result of the biopsy, clinical diagnosis was changed in 47% and treatment was changed in 33% of cases. Results either led to a specific clinical diagnosis or changed the diagnosis/treatment in 74% of patients. Positive family history of myopathy and findings of myopathic irritability on electromyography had a negative predictive value for diagnosis change.Conclusions:  Open muscle biopsy is useful in myopathy evaluation in the modern genetic era.
The CST3 B haplotype is associated with frontotemporal lobar degeneration
Authors: Benussi L. , Ghidoni R. , Galimberti D. , Boccardi M. , Fenoglio C. , Scarpini E. , Frisoni G. B. , Binetti G. 
Published: August 2009

Background and purpose:  Frontotemporal lobar degeneration (FTLD) is a common cause of early‐onset dementia. Given the role of cystatin C in brain neurodegeneration and neuroregeneration, the aim of this study was to determine whether the cystatin C gene (CST3) was genetically associated with FTLD.Methods:  Hundred and eighty‐six FTLD patients and 457 controls underwent CST3 analysis by PCR and KspI enzyme digestion.Results:  In FTLD patients negative for the presence of PGRN mutations, we found an over‐representation of the CST3 haplotype B [odds ratio (OR = 1.619, P = 0.002)] and of AB/BB genotypes (OR = 1.704, P = 0.008) in FTLD patients.Conclusions:  The present study indicated the CST3 B haplotype as a putative risk factor for FTLD in PGRN mutations negative patients. The reduced level of cystatin C, previously associated with the B haplotype, might represent the molecular factor responsible for the increased risk. Long‐term depletion of neurotrophic factors, such as cystatin C and progranulin proteins, seem to be a common theme in FTLD: boosting the expression of such proteins might be a promising therapeutic strategy for FTLD.
Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury‐induced neuropathic pain in rats
Authors: Jean Yen‐Hsuan , Chen Wu‐Fu , Sung Chun‐Sung , Duh Chang‐Yih , Huang Shi‐Ying , Lin Chan‐Shing , Tai Ming‐Hon , Tzeng Shun‐Fen , Wen Zhi‐Hong 
Published: August 2009

Background and purpose: Natural compounds obtained from marine organisms have received considerable attention as potential sources of novel drugs for treatment of human inflammatory diseases. Capnellene, isolated from the marine soft coralCapnella imbricate, 4,4,6a‐trimethyl‐3‐methylene‐decahydro‐cyclopenta[]pentalene‐2,3a‐diol (GB9) exhibited anti‐inflammatory actions on activated macrophagesin vitro. Here we have assessed the anti‐neuroinflammatory properties of GB9 and its acetylated derivative, acetic acid 3a‐hydroxy‐4,4,6a‐trimethyl‐3‐methylene‐decahydro‐cyclopenta[]pentalen‐2‐yl ester (GB10).Experimental approach: Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) in interferon‐γ (IFN‐γ)‐stimulated mouse microglial BV2 cells were measured by Western blot. Thein vivoeffects of these compounds were examined in the chronic constriction injury (CCI) rat model of neuropathic pain, measuring thermal hyperalgesia, and microglial activation and COX‐2 protein in lumbar spinal cord, by immunohistochemistry.Key results: In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX‐2, stimulated by IFN‐γ. Intrathecal administration of GB9 and GB10 inhibited CCI‐induced nociceptive sensitization and thermal hyperalgesia in a dose‐dependent manner. Intraperitoneal injection of GB9 inhibited CCI‐induced thermal hyperalgesia and also inhibited CCI‐induced activation of microglial cells and up‐regulation of COX‐2 in the dorsal horn of the lumbar spinal cord ipsilateral to the injury.Conclusion and implications: Taken together, these data indicate that the marine‐derived capnellenes, GB9 and GB10, had anti‐neuroinflammatory and anti‐nociceptive properties in IFN‐γ‐stimulated microglial cells and in neuropathic rats respectively. Therefore, capnellene may serve as a useful lead compound in the search for new therapeutic agents for treatment of neuroinflammatory diseases.
Early CK‐MB Elevations Predict Ischemic Events in Stable Chest Pain Patients
Authors: Hedges Jerris R. , Young Gary P. , Henkel Gary F. , Gibler W. Brian , Green Terrence R. , Swanson J. Robert 
Published: August 2009

ABSTRACT Objective: To demonstrate that creatine kinase‐MB fraction (CK‐MB) elevations within three hours of presentation in the emergency department (ED) are associated with subsequent ischemic events in clinically stable chest pain patients. Methods: Prospective cohort study at two university‐affiliated teaching hospitals. Participants were consenting ED chest pain patients 25 years old or older without evidence of rhythm or hemodynamic instability (n = 449). Exclusions included ST‐segment elevation ≥0.1 mV in ≥2 electrocardiogram leads, chest wall trauma, abnormal x‐ray studies, and incomplete data collection. Measurements included presenting and three‐hour CK‐MB levels, presenting ECG, initial clinical impression of coronary care unit need, and clinical follow up. Monitored adverse events included myocardial ischemia necessitating coronary angioplasty or cardiac bypass surgery, recurrent in‐hospital myocardial infarction, bradycardia requiring pacing, emergent cardioversion, cardiogenic shock, ventricular fibrillation, and death. Results: Overall, nine (2%) of 449 patients experienced an ischemic event within the first 48 hours. All nine patients required either coronary angioplasty or bypass surgery. Four (44%) of the nine patients with 48‐hour ischemic events had elevated CK‐MB levels. Of 23 patients who had complications within one week of ED presentation, seven (30%) had elevated ED CK‐MB levels. An elevated CK‐MB level was associated with an ischemic event both within 48 hours (risk ratio 9.5; 95% CI 2.7–33.7) and within one week (risk ratio 5.2; 95% CI 2.3–11.7). Conclusions: An elevated CK‐MB level within three hours of ED presentation is associated with a subsequent ischemic event in the clinically stable chest pain patient without ST‐segment elevation. However, the ED CK‐MB identifies only a minority of otherwise low‐risk patients who develop ischemic events; other markers for diagnosing myocardial ischemia in the ED are needed.