bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Expression of the Chromatin Remodeling Gene, SNF2L, Selectively Leads to DNA Damage, Growth Inhibition, and Cancer Cell Death
Authors: Ye Yin , Xiao Yi , Wang Wenting , Wang Qien , Yearsley Kurtis , Wani Altaf A. , Yan Qintao , Gao Jian-Xin , Shetuni Brandon S. , Barsky Sanford H.
Published: December 2009

SNF2L, a chromatin remodeling gene expressed in diverse tissues, cancers, and derived cell lines, contributes to the chromatin remodeling complex that facilitates transcription. Because of this wide expression, it has not been exploited as a cancer therapeutic target. However, based on our present studies, we find that cancer cells, although expressing SNF2L at similar levels as their normal counterparts, are sensitive to its knockdown. This is not observed when its imitation SWI ortholog, SNF2H, is inhibited. SNF2L siRNA inhibition using two different siRNAs separately reduced SNF2L transcript levels and protein in both normal and cancer lines, but only the cancer lines showed significant growth inhibition, DNA damage, a DNA damage response, and phosphorylation of checkpoint proteins and marked apoptosis. DNA damage and the damage response preceded apoptosis rather than being consequences of it. The damage response consisted of increased phosphorylation of multiple substrates including ATR, BRCA1, CHK1, CHK2, and H2AX. Both the total and phosphorylated levels of p53 increased. The downstream targets of p53, p21, GADD45A, and 14-3-3σ, were also upregulated. The alterations in checkpoint proteins included increased phosphorylated cdc2 but not Rb, which resulted in a modest G2-M arrest. Although apoptosis may be mediated by Apaf-1/caspase 9, other caspases could be involved. Other members of the chromatin remodeling or SWI/SNF gene families exhibited overall reduced levels of expression in the cancer lines compared with the normal lines. This raised the hypothesis that cancers are sensitive to SNF2L knockdown because, unlike their normal counterparts, they lack sufficient compensation from other family members. (Mol Cancer Res 2009;7(12):1984–99)
Gallic Acid Suppresses Lipopolysaccharide-Induced Nuclear Factor-κB Signaling by Preventing RelA Acetylation in A549 Lung Cancer Cells
Authors: Choi Kyung-Chul , Lee Yoo-Hyun , Jung Myung Gu , Kwon Seung Hyun , Kim Mi-Jeong , Jun Woo Jin , Lee Jeongmin , Lee Jae Myun , Yoon Ho-Geun
Published: December 2009

Although multiple studies have revealed that gallic acid plays an important role in the inhibition of malignant transformation, cancer development, and inflammation, the molecular mechanism of gallic acid in inflammatory diseases is still unclear. In this study, we identified gallic acid from Rosa rugosa as a histone acetyltransferase (HAT) inhibitor with global specificity for the majority of HAT enzymes, but with no activity toward epigenetic enzymes including sirtuin (silent mating type information regulation 2 homologue) 1 (S. cerevisiae), histone deacetylase, and histone methyltransferase. Enzyme kinetic studies indicated that gallic acid uncompetitively inhibits p300/CBP-dependent HAT activities. We found that gallic acid inhibits p300-induced p65 acetylation, both in vitro and in vivo, increases the level of cytosolic IκBα, prevents lipopolysaccharide (LPS)-induced p65 translocation to the nucleus, and suppresses LPS-induced nuclear factor-κB activation in A549 lung cancer cells. We have also shown that gallic acid treatment inhibits the acetylation of p65 and the LPS-induced serum levels of interleukin-6 in vivo. Importantly, gallic acid generally inhibited inflammatory responses caused by other stimuli, including LPS, IFN-γ, and interleukin-1β, and further downregulated the expression of nuclear factor-κB–regulated antiapoptotic genes. These results show the crucial role of acetylation in the development of inflammatory diseases. (Mol Cancer Res 2009;7(12):2011–21)
A Novel Inhibitor of DNA Polymerase β Enhances the Ability of Temozolomide to Impair the Growth of Colon Cancer Cells
Authors: Jaiswal Aruna S. , Banerjee Sanjeev , Panda Harekrushna , Bulkin Charles D. , Izumi Tadahide , Sarkar Fazlul H. , Ostrov David A. , Narayan Satya
Published: December 2009

The recent emerging concept to sensitize cancer cells to DNA-alkylating drugs is by inhibiting various proteins in the base excision repair (BER) pathway. In the present study, we used structure-based molecular docking of DNA polymerase β (Pol-β) and identified a potent small molecular weight inhibitor, NSC-666715. We determined the specificity of this small molecular weight inhibitor for Pol-β by using in vitro activities of APE1, Fen1, DNA ligase I, and Pol-β–directed single-nucleotide and long-patch BER. The binding specificity of NSC-666715 with Pol-β was also determined by using fluorescence anisotropy. The effect of NSC-666715 on the cytotoxicity of the DNA-alkylating drug temozolomide (TMZ) to colon cancer cells was determined by in vitro clonogenic and in vivo xenograft assays. The reduction in tumor growth was higher in the combination treatment relative to untreated or monotherapy treatment. NSC-666715 showed a high specificity for blocking Pol-β activity. It blocked Pol-β–directed single-nucleotide and long-patch BER without affecting the activity of APE1, Fen1, and DNA ligase I. Fluorescence anisotropy data suggested that NSC-666715 directly and specifically interacts with Pol-β and interferes with binding to damaged DNA. NSC-666715 drastically induces the sensitivity of TMZ to colon cancer cells both in in vitro and in vivo assays. The results further suggest that the disruption of BER by NSC-666715 negates its contribution to drug resistance and bypasses other resistance factors, such as mismatch repair defects. Our findings provide the “proof-of-concept” for the development of highly specific and thus safer structure-based inhibitors for the prevention of tumor progression and/or treatment of colorectal cancer. (Mol Cancer Res 2009;7(12):1973–83)
Ischemic Ileal Perforation in the Donor of Monochorionic Twins Complicated by Twin-Twin Transfusion Syndrome
Authors: Tsukimori Kiyomi , Yumoto Yasuo , Masumoto Kouji , Taguchi Tomoaki , Kondo Haruhiko , Sueishi Katsuo , Wake Norio
Published: December 2009

Twin-twin transfusion syndrome (TTTS) carries a significant risk of perinatal morbidity and mortality. Serial amnioreduction and fetoscopic laser photocoagulation have decreased perinatal mortality, thereby shifting attention towards short-term and long-term morbidity. Most morbidity occurs within the central nervous system. Ischemic lesions, however, such as congenital skin loss and limb necrosis may occur anywhere in the vasculature of recipient twins. Ischemia may also occur during serial amnioreduction and fetoscopic laser photocoagulation. We report a case of ileal perforation in the donor twin of untreated TTTS. Histopathology showed a focal area of erosion, possibly from ischemia. We also discuss the clinical features of ischemic intestinal complications of TTTS and review the literature.
Fetal Brain Hemodynamic Changes in Intrauterine Transfusion: Influence of Needle Puncture Site
Authors: Adama van Scheltema P.N. , Borkent S. , Sikkel E. , Oepkes D. , Vandenbussche F.P.H.A.
Published: December 2009

Objectives: Previous research has suggested that hemodynamic changes after in utero transfusion may be related to fetal stress. We tested the hypothesis that these hemodynamic changes are more pronounced when the needle is inserted in the fetal abdomen compared with the umbilical cord root. Methods: Most intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI) or in the intrahepatic portion of the umbilical vein (IHV). We analyzed prospectively collected data of all intrauterine blood transfusions (IUT) for fetal alloimmune anemia (from 2000 to 2003), for which complete data were available on needling site and middle cerebral artery (MCA) Doppler flow velocity measurements before and immediately after the procedure. Results: Data of 57 IUTs were included. In 32 patients, the transfusion was performed through the PCI and in 25 patients through the IHV. Mean pulsatility index (PI) in the PCI group was 2.0 before and 1.7 after IUT (p = 0.011), and in the IHV group 1.9 before and 1.5 after IUT (p = 0.001). In both groups, MCA PI decreased significantly, but there was no difference in decrease between the two groups (p = 0.99). Conclusions: In anemic fetuses undergoing transfusion, the observed fetal brain hemodynamic changes were independent of the site of needle insertion. The decrease in fetal MCA PI is therefore likely to be caused by the volume expansion.
Pregnancy Outcome in Maternal Crigler-Najjar Syndrome Type II: A Case Report and Systematic Review of the Literature
Authors: Passuello V. , Puhl A.G. , Wirth S. , Steiner E. , Skala C. , Koelbl H. , Kohlschmidt N.
Published: December 2009

Objective: To report a case of maternal Crigler-Najjar syndrome (CNS) type II in pregnancy, systematically review the literature for similar case reports, and to evaluate whether pregnancy is safe in patients with the disease. Data sources included the PubMed and uptodate databases. Results: A 37-year-old mother with CNS type II was treated with phenobarbital during her pregnancy and her bilirubin levels were monitored. Her newborn had mild direct hyperbilirubinemia, did not require any treatment and his postnatal follow-up showed normal growth and development as well as normal hearing. Conclusion: CNS type II is rare, and only a few pregnancies with this condition have been reported. Maternal treatment with phenobarbital lowers the unconjugated bilirubin and avoids fetal and newborn sequelae.
Single Cell Analysis of Mutations in the APC Gene
Authors: Mayer Veronika , Schoen Ulrike , Holinski-Feder Elke , Koehler Udo , Thalhammer Stefan
Published: December 2009

Introduction: Mutation analysis of inherited monogenic diseases is an important aspect of preimplantation genetic diagnosis. Familial adenomatous polyposis of the colon is an autosomal dominant inherited disorder caused by mutations in the tumor suppressor gene adenomatous polyposis coli (APC). A characteristic of this severe disease is the development of thousands of polyps in the colon which untreated evolve into malignant colon carcinomas. Here we present a novel approach for the establishment of mutation detection in the APC gene in single cells applicable for preimplantation genetic diagnosis. Methods: Single fixed lymphocytes were isolated via laser microdissection and transferred to reaction centers of planar chemically structured glass slides via a recently developed horizontal low-pressure single particle adsorbing transfer system (SPATS). A multiplex nested polymerase chain reaction protocol in a 1-μl reaction volume, followed by sequencing and fragment length analysis was applied in order to detect mutations in the APC gene. Results: Reliable isolation and transfer of single lymphocytes was demonstrated. High amplification efficiency and low allelic drop out (ADO) rates for polymorphic microsatellite markers and mutation specific amplification products of various mutations in the APC gene were obtained from fixed single cells. Conclusions: This novel nanotechnological downscaling approach enables a reliable validation of genetic testing using diploid single lymphocytes, and will open a wide range of single cell diagnostics.
A Holistic Approach to Androgen Deprivation Therapy: Treating the Cancer without Hurting the Patient
Authors: Tombal Bertrand
Published: December 2009

Introduction: Androgen deprivation therapy (ADT) for advanced prostate cancer can be associated with side effects which may negatively impact quality of life (QoL) and induce serious medical problems. Aim: The aim is to give practical recommendations on how to monitor and counsel patients and effectively manage side effects based on relevant original articles, review articles and abstracts. Results: Urologists should be aware of side effects and adapt their practice patterns to rapidly recognize these and administer appropriate treatment. Proper counseling of ADT-treated patients is needed to help them recognize and prevent and/or manage side effects. Patients should be encouraged to adopt a healthy lifestyle such as a healthy diet and physical exercise. In addition, bone mineral density and metabolic and cardiovascular parameters need to be carefully monitored. Conclusions: Urologists should take appropriate measures to prevent and manage ADT-related side effects to promote the general health and overall QoL of patients.
Preoperative Urodynamic Assessment in Patients with Spinal Cord Lesions Undergoing Sphincterotomy: Is Success Predictable?
Authors: Pannek Juergen , Hilfiker Roger , Goecking Konrad , Bersch Ulf
Published: December 2009

Objective: Sphincterotomy is a well-established therapeutic option in male patients with neurogenic bladder dysfunction and detrusor-sphincter-dyssynergia due to spinal cord lesions. Indication and prediction of treatment outcome, however, are mainly based on clinical parameters. We analyzed the clinical usefulness of preoperative urodynamic evaluation for the prediction of success in patients undergoing external sphincterotomy. Materials and Methods: In a retrospective study, residual urine, retrograde perfusion pressure (RESP) and detrusor leak point pressure (DLPP) in 62 male patients with spinal cord injury were assessed before sphincterotomy. Data were compared to surgical success evaluated by postoperative DLPP and residual urine. Results: Sphincterotomy was successful in 85.4% of our patients. In multivariate analysis, both preoperative DLPP and RESP were superior to measurement of residual urine concerning prediction of surgical success. However, these differences were not statistically significant. Conclusion: To our knowledge, this is the first study to evaluate preoperative predictors for surgical success in patients undergoing sphincterotomy. Although urodynamic evaluation is strongly advised prior to surgery in patients with spinal cord lesions, it improves prediction of success only marginally.
Cost-Effectiveness of Treating Ureteral Stones in a Taipei City Hospital: Shock Wave Lithotripsy versus Ureteroscopy plus Lithoclast
Authors: Huang Chi-Yi , Chen Shiou-Sheng , Chen Li-Kuei
Published: December 2009

Aim: To compare cost-effectiveness, success rates and sat isfaction score of ureteroscopic lithotripsy with lithoclast (URSL) and extracorporeal shock wave lithotripsy (ESWL) for ureteral stones in a Taipei City Hospital. Methods: This is a retrospective study. From July 1998 to June 2000, 448 patients who underwent treatment for ureteral stones were included. The patients were divided into two treatment groups according to the initial method adopted for the management of their stone. Medical records and hospital financial records were collected for costs of implementing each treatment program. The satisfaction scores of patients (rating from 0 to 10) were collected by telephone interviews. Success was defined as complete clearance of the stone or fragmentation of stones smaller than 2 mm by plain abdominal film and complete relief of symptoms after initial treatment. Results: A total of 360 patients were in the ESWL group (including 144 upper, 48 middle and 168 lower third stones) and 88 in the URSL group (including 28 upper, 24 middle and 36 lower third stones). The range of stone size was from 0.6 to 1.9 cm. The overall treatment cost was comparable in both groups with a trend for it to be higher in the ESWL group without reaching statistical significance (TWD 20,901.5 ± 8,911.3 vs. 19,876.1 ± 4,782.2). Stratified by the location of stone, the overall treatment cost was significantly higher in the ESWL group than in the URSL group for patients with upper third ureteral stones irrespective of stone size. The efficiency quotient for ESWL and URSL was 0.62 and 0.65, respectively. The success rate was significantly higher in the URSL group than in the ESWL group (89.8 vs. 71.7%). Satisfaction scores were similar for both groups with a trend to be higher in the ESWL group without reaching statistical significance (7.97 ± 1.01 vs. 7.53 ± 1.37). Conclusions: The overall treatment cost of patients with upper third ureteral stone was significantly higher in the ESWL group than in the URSL group, but the success rate was significantly higher in the URSL group than in the ESWL group.
Role of Testosterone/Estradiol Ratio in Predicting the Efficacy of Tamoxifen Citrate Treatment in Idiopathic Oligoasthenoteratozoospermic Men
Authors: Çakan Murat , Aldemir Mustafa , Topcuoglu Murat , Altuğ Uğur
Published: December 2009

Aim: It was the aim of this study to investigatethe effect ofalow testosterone/estradiol (T/E2) ratio and the normalization of this ratio by an aromatase inhibitor, anastrozole, on the treatment results of tamoxifen citrate (TAM) in idiopathic oligoasthenoteratozoospermic patients with a normal T/E2 ratio. Patients and Methods: 127 normogonadotropic men were included in this study. TAM (10 mg twice daily) was applied to 103 of the patients (group 1). The control group consisted of 25 patients who did not receive any treatment (group 2). After 3 months, TAM therapy was continued in 42 of the patients with a normal T/E2 ratio (group 1A). Of the remaining 61 patients with low ratios, 30 continued with TAM (group 1BTAM), while the remaining 31 patients underwent additional anastrozole therapy (1 mg/day) to TAM (group 1BANA). Results: In the 3rd month of the study, while the sperm concentration and motility were found significantly improved in group 1 (p < 0.05), they were significantly lower in groups 1BTAM and 1BANA than in group 1A (p < 0.01). In the 6th month of the study, the mean T/E2 ratio was normal in group 1A and group 1BANA, but was lower than normal ranges in group 1BTAM. The sperm concentration and motility significantly increased in groups 1A and 1BANA (p < 0.05). Conclusions: A significant decrease in the T/E2 ratio was seen in the majority of the patients during TAM treatment. Normalization of this ratio by addition of anastrozole to the treatment regimen improved the treatment outcomes. However, a placebo-controlled study is needed to confirm our results.
Influence of Cytokine Gene Polymorphisms on Prostate-Specific Antigen Recurrence in Prostate Cancer after Radical Prostatectomy
Authors: Lin Han-Ching , Liu Chia-Chu , Kang Wan-Yi , Yu Chia-Cheng , Wu Tony T. , Wang Jyh-Seng , Wu Wen-Jeng , Huang Chun-Hsiung , Wu Ming-Tsang , Huang Shu-Pin
Published: December 2009

Purpose: Evidence is accumulating indicating that chronic inflammation plays an important role in prostate cancer. We investigated the potential prognostic roles of IL-6, IL-8 and IL-10 polymorphisms in clinical localized prostate cancer after radical prostatectomy. Materials and Methods: A total of 116 clinically localized prostate cancer patients undergoing curative radical prostatectomy were included in this study. The IL-6, IL-8 and IL-10 polymorphisms were determined by the TaqMan real-time PCR method. Their prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using Kaplan-Meier analysis and Cox regression model. Results: The IL-6 polymorphism (rs2066992) T/G and G/G genotype cases were associated with a higher percentage of preoperative PSA levels of ≥10 ng/ml; higher risk of positive surgical margin, and higher risk of extraprostatic extension compared to the T/T genotype. The IL-10 polymorphism (rs1800871) A/A genotype was associated with a higher risk of PSA recurrence compared with the A/G + G/G genotypes and significantly poorer PSA-free survival (log-rank test, p = 0.019). After considering other covariates in a Cox proportional hazard model, the IL-10A/A genotype and high Gleason score (8–10) were still independent predictors of poor PSA-free survival. Conclusion: Our results suggest that the IL-10 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.
Prevalence of Hypertension and Associated Factors among Older Rural Adults: Results from Liaoning Province, China
Authors: Pang Wenyue , Li Zixu , Sun Zhaoqing , Zheng Liqiang , Zhang Xingang , Xu Changlu , Liu Shuangshuang , Li Jue , Hu Dayi , Sun Yingxian
Published: December 2009

Objective: The objective of the study was to estimate the prevalence of hypertension and associated factors among older rural adults in Liaoning Province, China. Subjects and Methods: The study was conducted in 2004–2006, using a multistage, stratified clustering sampling scheme to select a representative sample. A total of 10,065 adults aged 60 years or older were examined. A survey of blood pressure and associated factors was carried out. All data analyses were conducted using SPSS 11.5 statistical software package. Results: Overall, the prevalence rates of hypertension are 57, 64.4 and 64.9% for the age groups 60–69, 70–79 and ≥80 years, respectively. The prevalence of hypertension was positively correlated with age, female gender, Mongolian ethnicity, overweight and obesity, smoking and drinking, whereas income level was a protective factor for hypertension. The rates of awareness, treatment and control among older rural adults were very low (overall 35.2, 28.7 and 1.0%, respectively). Conclusion: Hypertension was highly prevalent among older rural adults in Liaoning Province, and it was associated with many factors. The percentages of hypertensives who were aware, treated, and controlled were very low. These data underscore the urgent need to strengthen the public health education and blood pressure monitoring system to better manage hypertension among older adults in rural China.
Evaluation of Somatic Development in Adult Patients with Previously Undiagnosed and/or Untreated Phenylketonuria
Authors: Mazur Artur , Jarochowicz Sabina , Sykut-Cegielska Jolanta , Gradowska Wanda , Kwolek Andrzej , Ołtarzewski Mariusz
Published: December 2009

Objective: To evaluate physical growth, development and nutritional status in adults with previously undiagnosed/ untreated phenylketonuria (PKU). Methods: Four hundred adults (201 females and 199 males) with severe intellectual disability who were born prior to compulsory neonatal screening (before 1976) and who resided in social welfare homes in southeastern Poland were screened for PKU. The screening was performed by blood test using a tandem mass spectrometry method (MS/MS) and was confirmed by analysis of organic acids in urine. Eleven were identified as previously undiagnosed and/or untreated PKU cases. They underwent an assessment of their somatic development/status. Results: Among the 11 PKU patients (4 females and 7 males) the following characteristics were observed: poor physical growth after somatic development (n = 8, 2 females aged 23 and 56 years and 6 males aged 28–59 years); decreased head circumference – microcephaly (n = 5, 1 female aged 56 years and 4 males aged 28–59 years); poor body height (n = 2, 1 female aged 23 years and 1 male aged 59 years); poor thoracic circumference (n = 9, 3 females aged 23–56 years and 6 males aged 28–59 years). Overall, body weight imbalance was noted in 9 (81.8%) patients and irregularity of body proportions in 6 (54.5%) patients. Conclusion: Our data showedthe importance of nutritional surveillance and impact of metabolic imbalance on physical growth and body stature in untreated PKU patients. We therefore recommend an adequate and individually planned introduction of dietary intervention among that group of patients in order to ameliorate its nutritional status, general fitness and health.
Influence of Sedation on Patients’ Perceptions and Recovery in Patients Undergoing Minor Perianal Procedures under Spinal Saddle Block
Authors: Schmittner Marc D. , Janke Christoph , Limmer Marc E. , Weiss Christel , Bussen Dieter G. , Beck Grietje C.
Published: December 2009

Objectives: Additional intra-operative sedation may help improve acceptability and comfort of anaesthesia in patients undergoing minor anorectal (perianal) procedures under spinal saddle block. This observational study was done to determine which patients request sedatives and to what extent sedatives affect the patients’ recovery. Subjects and Methods: During a 6-month period, 500 patients undergoing minor perianal procedures received 1.0 ml hyperbaric bupivacaine (0.5%). On request, a light sedation with propofol in bolus application was provided. Patients were evaluated postoperatively using a standardized questionnaire about their perceptions before, during and 48 h after the administration of anaesthesia. Results: More female (91/143, 63.6%) than male (136/259, 52.5%) patients (p = 0.0312) received sedation. Patients with sedation were significantly younger (46.7 ± 13.8 vs. 50 ± 13.8 years, p = 0.0171) and had a lower body mass index (BMI; 25.6 ± 4.3 vs. 27.5 ± 5.1, p < 0.0001). Time to mobilization and first micturition was significantly longer in patients with sedation (4.8 vs. 4.4 h, p = 0.0194 and 5.8 vs. 5.4 h, p = 0.0188), which was associated with a higher incidence of nausea (7.5 vs. 1.7%, p = 0.0083). Conclusions: Female gender, younger age, lower body weight and lower BMI were associated with higher subjective requirements for sedation. The use of sedation showed prolongation of time to first mobilization and micturition and a higher incidence of nausea.
Effects of Preoperative Gabapentin on Postoperative Nausea and Vomiting after Open Cholecystectomy: A Prospective Randomized Double-Blind Placebo-Controlled Study
Authors: Khademi Saeed , Ghaffarpasand Fariborz , Heiran Hamid Reza , Asefi Arshak
Published: December 2009

Objective: To evaluate the effect of gabapentin on the incidence and severity of postoperative nausea and vomiting (PONV) after open cholecystectomy. Subjects and Methods: A total of 90 patients scheduled for elective open cholecystectomy were randomly assigned to either a gabapentin group (600 mg, 2 h before surgery) or a placebo group. For the analysis, 1 patient was excluded from the gabapentin group and 2 patients from the placebo group. A standard technique was used for anesthesia. Pethidine and metoclopramide were used for postoperative management of pain and nausea/vomiting, respectively. The prevalence of PONV, its severity (measured on visual analogue scale, VAS), and total pethidine and metoclopramide use in the first 24 h after the operation were recorded. Results: There were no demographic differences between the two groups. Of the 44 patients given gabapentin, 16 (36.6%) and 28 of 43 (65.2%) placebo patients developed PONV; the difference was statistically significant (p = 0.02). However, there was no difference in the severity of PONV between the gabapentin and placebo groups (p = 0.12). Gabapentin patients used less pethidine (28.33 ± 129 mg) and metoclopramide (6.0 ±6.3 mg) than the placebo group (35.1 ± 15.1 and 9.33 ± 7.1 mg, respectively). The differences were statistically significant (pethidine: p = 0.002, metoclopramide: p = 0.033). However, gabapentin did not reduce postoperative pain significantly (p = 0.096). Conclusion: Our data show that gabapentin not only reduced PONV after open cholecystectomy, but also reduced the need for additional postoperative analgesics.
Effect of Raloxifene on Serum Lipids for Type 2 Diabetic Menopausal Women with or without Statin Treatment
Authors: Matsumura Mihoko , Monden Tsuyoshi , Nakatani Yuki , Shimizu Hiroaki , Domeki Nozomi , Yanagi Kazunori , Ikeda Shiori , Kawagoe Yoshiaki , Kasai Kikuo
Published: December 2009

Objective: Our aim was to investigate the effect of 1-year treatment with raloxifene, a selective estrogen receptor modulator, on plasma lipid profiles in Japanese postmenopausal type 2 diabetic patients. Subjects and Methods: A total of 43 Japanese women with postmenopausal osteoporosis and type 2 diabetes with serum low-density lipoprotein cholesterol (LDL-C) <3.59 mmol/l, serum triglyceride <1.68 mmol/l and serum high-density lipoprotein cholesterol (HDL-C) >1.03 mmol/l, who took 60 mg/day of raloxifene for 12 months, were enrolled. For analysis, they were divided into 2 groups: nonhyperlipidemia (n = 23) and hyperlipidemia treated with statin (n = 20). Results: Raloxifene treatment significantly induced a mean reduction in serum LDL-C from 2.90 to 2.36 and 2.67 mmol/l in the nonhyperlipidemia and statin-treated group, respectively. However, the reduction ratio of serum LDL-C showed a significant difference in the nonhyperlipidemia group (17%) compared to the statin-treated group (7%; p = 0.03). Although serum HDL-C showed an increase in both groups (from 1.45 to 1.58 vs. from 1.40 to 1.47 mmol/l), the increase ratio of serum HDL-C was not significant between the two groups. Raloxifene administration showed 15% reduction in the nonhyperlipidemia group (p = 0.02) and 13% reduction in the statin-treated group (p = 0.02) of urinary N-telopeptide of type I collagen. No significant change in blood HbA1c was observed in either group. Conclusion: The administration of raloxifene to type 2 diabetic women showed favorable efficacy on serum lipid profiles, particularly in patients without statin treatment.
Lymphocytic Infundibuloneurohypophysitis: Long-Term Follow-Up of a Case Cured with Glucocorticoid
Authors: Inaba Hidefumi , Suzuki Satoru , Shigematsu Satoshi , Takei Masahiro , Miyamoto Takahide , Takeda Teiji , Yamauchi Keishi , Hashizume Kiyoshi
Published: December 2009

Objective: To report a case of infundibuloneurohypophysitis treated with steroid. Clinical Presentation: A 65-year-old woman who was well until 4 weeks before admission and was not taking any medication presented with acute development of polydipsia and polyuria. Urinary volume was increased to 4,500 ml/day. She showed elevated serum osmolality and low urine osmolality, together with shortage of antidiuretic hormone. Magnetic resonance imaging (MRI) of the pituitary revealed marked nodular thickening of the neurohypophysis. Endocrinologically, anterior pituitary function appeared normal. Based on these examinations, she was diagnosed as having central diabetes insipidus due to lymphocytic infundibuloneurohypophysitis. Intervention: Prednisolone (1 mg/kg/day, p.o.) and D-deaminovasopressin (5 μg/day, intranasal) were commenced. Ten days after the administration of the agents, MRI showed a dramatic improvement in the thickening of the neurohypophysis. Ten weeks later, abnormalities found in earlier MRI had disappeared. The drugs were withdrawn gradually, and diabetes insipidus ceased 25 weeks later. Recurrence was not seen in the subsequent MRI, and the function of the posterior pituitary gland was completely normalized even 7 years after discontinuation of treatments. Conclusion: This case shows that noninvasive diagnosis and appropriate steroid administration can effectively cure lymphocytic infundibuloneurohypophysitis; it is recommended with long-term follow-up.
Magnetic Resonance Imaging in Lewy Body Dementias
Authors: Watson Rosie , Blamire Andrew M. , O'Brien John T.
Published: December 2009

Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) share common clinical, neuropsychological and pathological features. In clinical diagnosis, distinguishing between these conditions and other dementia subtypes such as Alzheimer’s disease (AD) can be difficult. Despite the development of consensus diagnostic criteria, sensitivity for diagnosis remains low, especially outside specialist centres. Neuroimaging techniques using magnetic resonance (MR) can assess changes in structure, microstructure through diffusion tensor imaging and metabolism using spectroscopy and cerebral perfusion. Identification of such changes may contribute to our understanding of the disease process, assist in refining ante-mortem diagnosis and allow disease progression to be measured. This may be both clinically useful and a tool for assessing outcome in therapeutic trials. DLB and PDD share a similar pattern of MRI changes including global brain volume loss, a predominantly subcortical pattern of cerebral atrophy and structural preservation of the medial temporal lobe compared to AD. This review summarises the application and findings from MR studies in DLB and PDD to provide further insight into the similarities between the conditions, highlight the potential for the clinical application of MR techniques and outline promising areas for further research.
A New Model for Blunt Liver Injuries in the Swine
Authors: Grottke O. , Braunschweig T. , Philippen B. , Gatzweiler K.H. , Gronloh N. , Staat M. , Rossaint R. , Tolba R.
Published: December 2009

Background: To elaborate the impact of new haemostatic agents we developed an instrument for the pressure-controlled induction of blunt liver injuries in a porcine animal model. Materials and Methods: A dilutional coagulopathy of 80% of animal blood volume was induced in 9 anaesthetized pigs. Animals were randomly assigned to be injured with a force of 112 Newton (N) (n = 1), 224 ± 19 N (n = 4) or 355 ± 35 N (n = 4). The impact of injury was measured by blood loss, survival time and coagulation parameters. Liver histology was obtained to evaluate the degree of liver injury. Results: The profound haemodilution resulted in a significant alteration of all coagulation parameters. After inflicting the injury with 355 ± 35 N, both the survival time (30 ± 9 min; p = 0.006) and blood loss (68 ± 16 ml min–1, p = 0.002) were significantly different as compared to injuries with 224 ± 19 N (survival time: 76 ± 20 min, blood loss: 23 ± 4 ml min–1). In contrast, an injury with 112 N led to an insignificant blood loss of only 239 ml. Conclusion: We developed a pressure-controlled clamp that allows for the induction of blunt liver traumas with highly reproducible injuries with a positive correlation with blood loss and survival.
Enhancement Effect of Adenovirus-Mediated Antisense c-myc and Caffeine on the Cytotoxicity of Cisplatin in Osteosarcoma Cell Lines
Authors: Xie Xian-kuan , Yang Di-sheng , Ye Zhao-ming , Tao Hui-min
Published: December 2009

Aims: Studies on cancer biology have shown that overexpression of oncogenes (with or without functional loss of tumor suppressor genes), which is responsible for the progression of human malignancies via a multistep process, may be reduced by antisense technology. Caffeine enhances the effect of cisplatin (CDDP) chemotherapy on osteosarcoma cells. We constructed the recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment and investigated the synergic effect of caffeine and Myc-AS on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin. Methods: The recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment was constructed by cloning c-myc cDNA of about 750 bp in a reverse direction into adenovirus vector, then undergoing recombination, amplification and complementation in vivo. Myc-AS and caffeine were used either alone or in combination with CDDP to treat osteosarcoma MG-63 cells in vitro. Western blot, MTT, flow cytometry (FCM) and electron microscopy were used to evaluate the expression of c-myc protein, tumor cell proliferation in vitro and apoptosis and to perform cell cycle analysis. Results: Myc-AS encoding antisense c-myc fragment was obtained with a titer of 2 × 109 pfu/ml. Myc-AS downregulated the expression of c-myc protein after transfecting MG-63 cells for 48 h, induced tumor cell apoptosis and inhibited tumor cell proliferation in vitro. Myc-AS or caffeine can enhance the cytotoxic effects of 2.0 and 5.0 μg/ml CDDP on MG-63 cells. Moreover, the significantly enhancing effect of the Myc-AS-caffeine combination on CDDP chemotherapy of MG-63 cells was not restricted to apoptosis but also decreased tumor cell proliferation in vitro. Expression of the apoptosis-associated bcl-2 gene was downregulated and bax was upregulated, with no changes in E2F-1 expression. FCM analysis showed that CDDP treatment induced a block in S phase, and caffeine reversed this block and accelerated cell progression through the S phase. Conclusions: Myc-AS can induce obvious G2/M phase arrest in transfected cells. Myc-AS combined with caffeine can enhance apoptosis induction and chemotherapeutic effects of CDDP on osteosarcoma MG-63 cells.
Smoking and Alcohol Intake in Severely Affected Patients with Psoriasis in Germany
Authors: Gerdes S. , Zahl V.A. , Weichenthal M. , Mrowietz U.
Published: December 2009

Background: Smoking and alcohol may contribute as triggering factors for psoriasis and are substantial for managing severely affected psoriasis patients. Objectives: To evaluate the general state of smoking and alcohol intake in a group of hospitalized, severely affected patients with psoriasis in comparison with the general population of Germany. Methods: A retrospective, multicentre study analysing data from 1,203 patients with severe psoriasis was performed. Results: 43.3% of all patients were found to be active smokers (males: 46.6%; females: 39.2%) with a higher likelihood as the control group (odds ratio, OR, 2.08, 95% confidence interval, CI, 1.81–2.39; p < 0.0001). 14.9% of all patients were found to be excessive drinkers (female patients: 5.5%; male patients: 22.3%), more likely than the control group (OR 3.10, 95% CI 2.53–3.80; p < 0.0001); males had an OR of 2.86 (95% CI 2.29–3.56; p < 0.0001) and females an OR of 5.12 (95% CI 3.12–8.39; p < 0.0001). Conclusion: Smoking and alcohol intake are independently associated with severe forms of psoriasis. Disease severity is correlated with smoking in both genders as well as with alcohol intake in female patients.
Impact of Multiphase 68Ga-DOTATOC-PET/CT on Therapy Management in Patients with Neuroendocrine Tumors
Authors: Ruf Juri , Heuck Friederike , Schiefer Jan , Denecke Timm , Elgeti Florian , Pascher Andreas , Pavel Marianne , Stelter Lars , Kropf Siegfried , Wiedenmann Bertram , Amthauer Holger
Published: December 2009

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29–79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion:68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.
Clinical Characteristics and Genetic Background of Congenital Long-QT Syndrome Diagnosed in Fetal, Neonatal, and Infantile Life
Authors: Horigome Hitoshi , Nagashima Masami , Sumitomo Naokata , Yoshinaga Masao , Ushinohama Hiroya , Iwamoto Mari , Shiono Junko , Ichihashi Koh , Hasegawa Satoshi , Yoshikawa Tadahiro , Matsunaga Tamotsu , Goto Hiroko , Waki Kenji , Arima Masaki , Takasugi Hisashi , Tanaka Yasuhiko , Tauchi Nobuo , Ikoma Masanobu , Inamura Noboru , Takahashi Hideto , Shimizu Wataru , Horie Minoru
Published: December 2009

Background—

Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence.

Methods and Results—

Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of β-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator.

Conclusions—

Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.
Magnetic Resonance Tissue Phase Mapping of Myocardial Motion
Authors: Föll Daniela , Jung Bernd , Schilli Elfriede , Staehle Felix , Geibel Annette , Hennig Jürgen , Bode Christoph , Markl Michael
Published: December 2009

Background—

An exact understanding of normal age- and gender-matched regional myocardial performance is an essential perquisite for the diagnosis of heart disease. Magnetic resonance phase-contrast imaging (tissue phase mapping) enabling the analysis of segmental, 3-directional myocardial velocities with high temporal resolution (13.8 ms) was used to assess left ventricular motion.

Methods and Results—

Radial, long-axis, and rotational myocardial velocities were acquired in 58 healthy volunteers (3 age groups, 29 women) in left ventricular basal, midventricular, and apical short-axis locations. For increased age, reduced (
P
<0.003) and prolonged long-axis and radial velocities (
P
<0.05) during diastole and reduced long-axis velocities (
P
<0.001) and apical rotation (
P
<0.005) during systole were found for both genders. Women demonstrated a reduced systolic twist (
P
=0.009), apical rotation (
P
=0.01), and systolic radial velocities (
P
<0.02) compared with men. Segmental analysis of long-axis motion with aging revealed differences in regional reduction of systolic (lateral 52% versus 30%) and diastolic (lateral 57% versus 41%) velocities in women compared with men. In basal segments, young women demonstrated higher long-axis velocities (+11% during diastole) than men, whereas this difference was reversed in older subjects (same segments, −20%). In addition, increased age resulted in a prolonged time to peak diastolic apical rotation (
P
<0.04) in women compared with men.

Conclusions—

Age and gender strongly influence regional myocardial motion. Tissue phase mapping provides a comprehensive quantitative analysis of all myocardial velocities with high temporal and spatial resolution. The knowledge of the detected age- and gender-related differences in myocardial motion is fundamental for further investigations of cardiac disease.

Clinical Trial Registration—

http://www.zks.uni-freiburg.de/uklreg/php/suchergebnis_all.php. Identifier: UKF001739
Determinants of Cardiac Catheterization Use in Older Medicare Patients With Acute Myocardial Infarction
Authors: Ko Dennis T. , Ross Joseph S. , Wang Yongfei , Krumholz Harlan M.
Published: December 2009

Background—

Cardiac catheterization is substantially underused among higher-risk patients with acute myocardial infarction (AMI) with appropriate indications but overused among patients with inappropriate indications. We sought to determine the importance of anticipated benefit and anticipated harm on the use of cardiac catheterization among older patients with AMI.

Methods and Results—

We performed an analysis of Medicare fee-for-service beneficiaries hospitalized with an AMI between 1998 and 2001. Multivariate models were developed to determine relative importance of anticipated benefit (baseline cardiovascular risk), anticipated harm (bleeding risk, comorbidities), and demographic factors (age, sex, race, regional invasive intensity) in predicting cardiac catheterization use within 60 days of AMI admission. Analyses were stratified by American College of Cardiology/American Heart Association class I or II as appropriate, and class III as inappropriate. Determinants of reduced likelihood of cardiac catheterization among 42 241 AMI patients with appropriate indications included (in order of importance) older age (likelihood χ
2
=1309.5), higher bleeding risk score (likelihood χ
2
=471.2), more comorbidities (likelihood χ
2
=276.6), female sex (likelihood χ
2
=162.9), hospitalization in low (likelihood χ
2
=67.9) or intermediate intensity invasive regions (likelihood χ
2
=22.4) (all
P
<0.001), and baseline cardiovascular risk (likelihood χ
2
=6.4,
P
=0.01). Among 2398 AMI patients with inappropriate indications, significant determinants of greater procedure likelihood included younger age, male sex, lower bleeding risk score, and fewer comorbidities.

Conclusions—

Regardless of the procedure indication, the decision to perform cardiac catheterization in this population appears largely driven by demographic factors and potential harm rather than potential benefit of the procedure.
Evaluating Regional Accent Variation in Standard Dutch
Authors: Grondelaers Stefan , van Hout Roeland , Steegs Mieke
Published: December 2009

This article investigates native speakers’ attitudes toward accent variation in Netherlandic Standard Dutch. Adopting the speaker evaluation paradigm, a demographically controlled sample of listener-judges rated spontaneous speech samples that are representative of four regions in the Netherlands, and from which potentially competing linguistic cues (e.g., pitch and intonation) had not been removed. Speech stimuli were rated on a set of scales integrated from among previous studies conducted in the Low Countries. Regionally marked standard accents activated distinct attitude profiles that were largely invariant with respect to the age, gender, level of education, and regional provenance of the listener-judges. It is argued that these regionally flavored standard varieties were found to be more than social categorization cues: Data reveal that an accent elicits perceptions of its so-called intrinsic euphony and norm status in addition to the status and integrity of its speakers.