bluuebunny/crossref_metadata_2025 huggingface dataset:
FPGA Interconnect Topologies Exploration
Authors: Marrakchi Zied , Mrabet Hayder , Farooq Umer , Mehrez Habib
Published: October 2009

This paper presents an improved interconnect network for Tree‐based FPGA architecture that unifies two unidirectional programmable networks. New tools are developed to place and route the largest benchmark circuits, where different optimization techniques are used to get an optimized architecture. The effect of variation in LUT and cluster size on the area, performance, and power of the Tree‐based architecture is analyzed. Experimental results show that an architecture with LUT size 4 and arity size 4 is the most efficient in terms of area and static power dissipation, whereas the architectures with higher LUT and cluster size are efficient in terms of performance. We also show that unifying a Mesh with this Tree topology leads to an architecture which has good layout scalability and better interconnect efficiency compared to VPR‐style Mesh.
Tropomyosin Period 3 Is Essential for Enhancement of Isometric Tension in Thin Filament-Reconstituted Bovine Myocardium
Authors: Kawai Masataka , Lu Xiaoying , Hitchcock-DeGregori Sarah E. , Stanton Kristen J. , Wandling Michael W.
Published: October 2009

Tropomyosin (Tm) consists of 7 quasiequivalent repeats known as “periods,” and its specific function may be associated with these periods. To test the hypothesis that either period 2 or 3 promotes force generation by inducing a positive allosteric effect on actin, we reconstituted the thin filament with mutant Tm in which either period 2 (Δ2Tm) or period 3 (Δ3Tm) was deleted. We then studied: isometric tension, stiffness, 6 kinetic constants, and the pCa-tension relationship. N-terminal acetylation of Tm did not cause any differences. The isometric tension inΔ2Tm remained unchanged, and was reduced to ~60% inΔ3Tm. Although the kinetic constants underwent small changes, the occupancy of strongly attached cross-bridges was not much different. The Hill factor (cooperativity) did not differ significantly betweenΔ2Tm (1.79±0.19) and the control (1.73±0.21), orΔ3Tm (1.35±0.22) and the control. In contrast, pCa50decreased slightly inΔ2Tm (5.11±0.07), and increased significantly inΔ3Tm (5.57±0.09) compared to the control (5.28±0.04). These results demonstrate that, when ions are present at physiological concentrations in the muscle fiber system, period 3 (but not period 2) is essential for the positive allosteric effect that enhances the interaction between actin and myosin, and increases isometric force of each cross-bridge.
Anticancer Chemotherapy Inhibits MHC Class I–Related Chain A Ectodomain Shedding by Downregulating ADAM10 Expression in Hepatocellular Carcinoma
Authors: Kohga Keisuke , Takehara Tetsuo , Tatsumi Tomohide , Miyagi Takuya , Ishida Hisashi , Ohkawa Kazuyoshi , Kanto Tatsuya , Hiramatsu Naoki , Hayashi Norio
Published: October 2009

MHC class I–related chain A (MICA) is a ligand for the NKG2D-activating immunoreceptor that mediates activation of natural killer (NK) cells. The ectodomain of MICA is shed from tumor cells, which may be an important means of evading antitumor immunity. We previously reported that patients with hepatocellular carcinoma (HCC) display high levels of soluble MICA in circulation, which could be downregulated by chemotherapy. The present study shows that anti-HCC drugs suppress MICA ectodomain shedding by inhibiting expression of a disintegrin and metalloproteinase 10 (ADAM10). Both ADAM10 and CD44, a typical substrate of the ADAM10 protease, were expressed in human HCC tissues and HCC cells but not in normal liver tissues or cultured hepatocytes. Small interfering RNA–mediated knockdown experiments revealed that ADAM10 is a critical sheddase for both MICA and CD44 in HCC cells. Of interest is the finding that epirubicin clearly downregulated ADAM10 expression and MICA shedding in HCC cells; its suppressive effect on MICA shedding was abolished in ADAM10-depleted cells. Epirubicin treatment also enhanced the NKG2D-mediated NK sensitivity of HCC cells. Patients with HCC had significantly higher levels of serum-soluble CD44, which correlated well with serum-soluble MICA levels, thus suggesting a close link between ADAM10 activity and MICA shedding in these patients. Soluble MICA and CD44 levels were downregulated with a significant correlation in patients treated by transarterial chemoembolization using epirubicin. In conclusion, anticancer drugs can modulate expression of ADAM10, which is critically involved in MICA ectodomain shedding. Epirubicin therapy may have a previously unrecognized effect on antitumor immunity in HCC patients. [Cancer Res 2009;69(20):8050–7]
A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients with Solid Malignancies
Authors: Burris Howard A. , Taylor Charles W. , Jones Suzanne F. , Koch Kevin M. , Versola Melissa J. , Arya Niki , Fleming Ronald A. , Smith Deborah A. , Pandite Lini , Spector Neil , Wilding George
Published: October 2009

Purpose: This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence of clinical activity following once or twice daily administration of lapatinib in patients with solid malignancies.

Experimental Design: Cancer patients (n = 81) received oral doses of lapatinib ranging from 175 to 1,800 mg once daily or 500 to 900 mg twice daily. Clinical assessments of safety and antitumor activity were recorded and blood was sampled for pharmacokinetic assessments. The effect of a low-fat meal on lapatinib pharmacokinetics was assessed in a subset of patients.

Results: Lapatinib was well tolerated, such that dose escalation was limited at 1,800 mg once daily only by pill burden. Twice-daily dosing was implemented to further explore tolerability, and was limited by diarrhea to 500 mg twice daily. The most commonly reported adverse events with once-daily dosing were diarrhea (48%), nausea (40%), rash (40%), and fatigue (38%) and with twice-daily dosing were diarrhea (85%), rash (54%), and nausea (34%). Lapatinib serum concentrations accumulated upon repeated dosing, increasing nearly in proportion with dose, and were significantly increased when dosed with food or administered twice daily. One patient with head and neck cancer achieved a confirmed complete response and 22 patients had stable disease of ≥8 weeks including three patients with stable disease of >10 months (renal, lung, and salivary gland cancers).

Conclusion: Lapatinib was well tolerated following once and twice daily administration. Systemic exposure to lapatinib was dependent on the dose, duration and frequency of dosing, and prandial state. Clinical activity was observed. (Clin Cancer Res 2009;15(21):6702–8)
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Reverses Mesenchymal to Epithelial Phenotype and Inhibits Metastasis in Inflammatory Breast Cancer
Authors: Zhang Dongwei , LaFortune Tiffany A. , Krishnamurthy Savitri , Esteva Francisco J. , Cristofanilli Massimo , Liu Ping , Lucci Anthony , Singh Balraj , Hung Mien-Chie , Hortobagyi Gabriel N. , Ueno Naoto T.
Published: October 2009

Purpose: Inflammatory breast cancer (IBC) is a rare but aggressive type of advanced breast cancer. Epidermal growth factor receptor (EGFR) expression is an independent poor prognostic factor in IBC. The purpose of this study was to determine the effect on IBC tumorigenicity and metastasis of blocking the EGFR pathway.

Experimental Design: IBC cell lines, which express high level of EGFR, were treated with EGFR small interfering RNA and with the EGFR tyrosine kinase inhibitor erlotinib. The role of EGFR in IBC cell proliferation, motility, invasiveness, and change of the expression levels of epithelial-mesenchymal transition markers was examined. The role of extracellular signal–regulated kinase (ERK)-1/2 in erlotinib activity was also studied. The activity of erlotinib in tumor growth and metastasis was examined in an orthotopic xenograft model of IBC.

Results: Erlotinib inhibited proliferation and anchorage-independent growth of IBC cells, and this inhibition was ERK dependent. Erlotinib inhibited cell motility and invasiveness and reversed the mesenchymal phenotype of IBC cells to epithelial phenotype in three-dimensional culture. Erlotinib dramatically inhibited IBC tumor growth in a xenograft model. Interestingly, erlotinib inhibited spontaneous lung metastasis, even at a low dose that had no significant effect on primary tumor growth. These erlotinib-treated tumors were converted to epithelial phenotype from mesenchymal phenotype.

Conclusions: The EGFR pathway is involved in tumor growth and metastasis of IBC. Targeting EGFR through the ERK pathway may represent an effective therapeutic approach to suppress tumorigenicity and prevent metastasis in EGFR-expressing IBC. (Clin Cancer Res 2009;15(21):6639–48)
Lymphocytic Reaction to Colorectal Cancer Is Associated with Longer Survival, Independent of Lymph Node Count, Microsatellite Instability, and CpG Island Methylator Phenotype
Authors: Ogino Shuji , Nosho Katsuhiko , Irahara Natsumi , Meyerhardt Jeffrey A. , Baba Yoshifumi , Shima Kaori , Glickman Jonathan N. , Ferrone Cristina R. , Mino-Kenudson Mari , Tanaka Noriko , Dranoff Glenn , Giovannucci Edward L. , Fuchs Charles S.
Published: October 2009

Purpose: Host immune response to tumor may be an important prognostic factor for colon cancer patients. However, little is known on prognostic significance of histopathologic lymphoid reaction to tumor, independent of the number of lymph nodes examined and tumoral molecular alterations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), both of which are associated with lymphocytic reaction and clinical outcome.

Experimental Design: Using 843 colorectal cancer patients in two independent prospective cohorts, we examined patient prognosis in relation to four components of lymphocytic reaction (i.e., Crohn's-like reaction, peritumoral reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes) and overall lymphocytic score (0-12). CIMP was determined using eight markers including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1. Cox proportional hazard models computed hazard ratio for mortality, adjusted for covariates including tumor stage, body mass index, lymph node count, KRAS, BRAF, p53, cyclooxygenase-2 (PTGS2), MSI, CIMP, and LINE-1 methylation.

Results: Increasing overall lymphocytic reaction score including tumor-infiltrating lymphocytes was associated with a significant improvement in colorectal cancer–specific and overall survival (log-rank P < 0.003). These findings remained significant (adjusted hazard ratio estimates, 0.49-0.71; Ptrend < 0.009) in multivariate models that adjusted for covariates, including body mass index, MSI, CIMP, LINE-1 hypomethylation, and cyclooxygenase-2. The beneficial effect of tumoral lymphocytic reaction was consistent across strata of clinical, pathologic, and molecular characteristics.

Conclusions: Lymphocytic reactions to tumor were associated with improved prognosis among colorectal cancer patients, independent of lymph node count and other clinical, pathologic, and molecular characteristics. (Clin Cancer Res 2009;15(20):6412–20)
GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers
Authors: Sabbatini Peter , Korenchuk Susan , Rowand Jason L. , Groy Arthur , Liu Qi , Leperi Dominic , Atkins Charity , Dumble Melissa , Yang Jingsong , Anderson Kelly , Kruger Ryan G. , Gontarek Richard R. , Maksimchuk Kenneth R. , Suravajjala Sapna , Lapierre Russell R. , Shotwell J. Brad , Wilson Joseph W. , Chamberlain Stanley D. , Rabindran Sridhar K. , Kumar Rakesh
Published: October 2009

The insulin-like growth factor-I receptor (IGF-IR) signaling pathway is activated in various tumors, and inhibition of IGF-IR kinase provides a therapeutic opportunity in these patients. GSK1838705A is a small-molecule kinase inhibitor that inhibits IGF-IR and the insulin receptor with IC50s of 2.0 and 1.6 nmol/L, respectively. GSK1838705A blocks the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiple myeloma and Ewing's sarcoma, and retards the growth of human tumor xenografts in vivo. Despite the inhibitory effect of GSK1838705A on insulin receptor, minimal effects on glucose homeostasis were observed at efficacious doses. GSK1838705A also inhibits the anaplastic lymphoma kinase (ALK), which drives the aberrant growth of anaplastic large-cell lymphomas, some neuroblastomas, and a subset of non–small cell lung cancers. GSK1838705A inhibits ALK, with an IC50 of 0.5 nmol/L, and causes complete regression of ALK-dependent tumors in vivo at well-tolerated doses. GSK1838705A is therefore a promising antitumor agent for therapeutic use in human cancers. [Mol Cancer Ther 2009;8(10):2811–20]
A Novel DNMT3B Splice Variant Expressed in Tumor and Pluripotent Cells Modulates Genomic DNA Methylation Patterns and Displays Altered DNA Binding
Authors: Gopalakrishnan Suhasni , Van Emburgh Beth O. , Shan Jixiu , Su Zhen , Fields C. Robert , Vieweg Johannes , Hamazaki Takashi , Schwartz Philip H. , Terada Naohiro , Robertson Keith D.
Published: October 2009

DNA methylation is an epigenetic mark essential for mammalian development, genomic stability, and imprinting. DNA methylation patterns are established and maintained by three DNA methyltransferases: DNMT1, DNMT3A, and DNMT3B. Interestingly, all three DNMTs make use of alternative splicing. DNMT3B has nearly 40 known splice variants expressed in a tissue- and disease-specific manner, but very little is known about the role of these splice variants in modulating DNMT3B function. We describe here the identification and characterization of a novel alternatively spliced form of DNMT3B lacking exon 5 within the NH2-terminal regulatory domain. This variant, which we term DNMT3B3Δ5 because it is closely related in structure to the ubiquitously expressed DNMT3B3 isoform, is highly expressed in pluripotent cells and brain tissue, is downregulated during differentiation, and is conserved in the mouse. Creation of pluripotent iPS cells from fibroblasts results in marked induction of DNMT3B3Δ5. DNMT3B3Δ5 expression is also altered in human disease, with tumor cell lines displaying elevated or reduced expression depending on their tissue of origin. We then compared the DNA binding and subcellular localization of DNMT3B3Δ5 versus DNMT3B3, revealing that DNMT3B3Δ5 possessed significantly enhanced DNA binding affinity and displayed an altered nuclear distribution. Finally, ectopic overexpression of DNMT3B3Δ5 resulted in repetitive element hypomethylation and enhanced cell growth in a colony formation assay. Taken together, these results show that DNMT3B3Δ5 may play an important role in stem cell maintenance or differentiation and suggest that sequences encoded by exon 5 influence the functional properties of DNMT3B. (Mol Cancer Res 2009;7(10):1622–34)
A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells
Authors: Hofmann Marco H. , Heinrich Jochen , Radziwil Gerald , Moelling Karin
Published: October 2009

The noncoding RNA miR-125b has been described to reduce ErbB2 protein expression as well as proliferation and migration of cancer cell lines. As additional target of miR-125b, we identified the c-raf-1 mRNA by sequence analysis. We designed a short hairpin-looped oligodeoxynucleotide (ODN) targeted to the same 3′ untranslated region of c-raf-1 mRNA as miR-125b. The fully complementary ODN antisense strand is linked to a second strand constituting a partially double-stranded structure of the ODN. Transfection of the c-raf-1–specific ODN (ODN-Raf) in a breast cancer cell line reduced the protein levels of C-Raf, ErbB2, and their downstream effector cyclin D1 similar to miR-125b. MiR-125b as well as ODN-Raf showed no effect on the c-raf-1 mRNA level in contrast to small interfering RNA. Unlike miR-125b, ODN-Raf induced a cytopathic effect. This may be explained by the structural properties of ODN-Raf, which can form G-tetrads. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. Both features may be useful to interfere with tumor growth. (Mol Cancer Res 2009;7(10):1635–44)
Amplification of Lipopolysaccharide-Induced Cytokine Synthesis in Non–Small Cell Lung Cancer/Neutrophil Cocultures
Authors: Grandel Ulrich , Heygster Diana , Sibelius Ulf , Fink Ludger , Sigel Stefanie , Seeger Werner , Grimminger Friedrich , Hattar Katja
Published: October 2009

Proinflammatory cytokines are centrally involved in tumor progression and survival in non–small cell lung cancer, and both the presence of infiltrating neutrophils and bacterial infection in the lung may indicate a poor prognosis. Against this background, we investigated the effect of the bacterial cell wall component lipopolysaccharide (LPS) on interleukin (IL)-6 and IL-8 synthesis in the non–small cell lung cancer line A549 and in A549-neutrophil cocultures. The LPS induced a dose-dependent and time-dependent release of IL-8 from A549 cells, whereas IL-6 could not be detected. Interestingly, in A549-neutrophil cocultures, IL-8 synthesis was massively amplified and IL-6 was also released, compared with the respective monocultures. The A549 cells were identified as the primary cellular source of these cytokines, as enhanced cytokine mRNA transcription was detected in this cell type, although not in neutrophils in the coculture system. Experiments done in transwells indicated that direct cell-cell contact was a prerequisite for the increased cytokine generation. Inhibition of tumor necrosis factor-α bioactivity by neutralizing antibodies and blocking cyclooxygenase-2 activity blunted the enhanced cytokine generation in the coculture system. Amplification of LPS-induced cytokine secretion could be reproduced when the small cell lung cancer cell line H69 was cocultured with neutrophils. When the Gram-positive cell wall component lipoteichoic acid was used instead of LPS, cytokine synthesis was also amplified in A549-neutrophil cocultures, to a similar extent to that observed with LPS. These data indicate that interaction between bacterial pathogens, neutrophils, and tumor cells might amplify the release of proinflammatory cytokines which may promote tumor growth in vivo. (Mol Cancer Res 2009;7(10):1729–35)
Expression of PGK1 by Prostate Cancer Cells Induces Bone Formation
Authors: Jung Younghun , Shiozawa Yusuke , Wang Jianhua , Wang Jingcheng , Wang Zhuo , Pedersen Elisabeth A. , Lee Clara H. , Hall Christopher L. , Hogg Phillip J. , Krebsbach Paul H. , Keller Evan T. , Taichman Russell S.
Published: October 2009

Prostate cancer (PCa) is one of the solid tumors that metastasize to the bone. Once there, the phenotype of the bone lesions is dependent upon the balance between osteoblastogenesis and osteoclastogenesis. We previously reported that overexpression of phosphoglycerate kinase 1 (PGK1) in PCa cell lines enhanced bone formation at the metastatic site in vivo. Here, the role of PGK1 in the bone formation was further explored. We show that PCa-derived PGK1 induces osteoblastic differentiation of bone marrow stromal cells. We also found that PGK1 secreted by PCa inhibits osteoclastogenesis. Finally, the expression levels of the bone-specific markers in PCa cells were higher in cells overexpressing PGK1 than controls. Together, these data suggest that PGK1 secreted by PCa regulates bone formation at the metastatic site by increasing osteoblastic activity, decreasing osteoclastic function, and expressing an osteoblastic phenotype by PCa cells. (Mol Cancer Res 2009;7(10):1595–604)
Placental Immaturity, Endocardial Fibroelastosis and Fetal Hypoxia
Authors: Perez Marie-Hélène , Boulos Tatiana , Stucki Pascal , Cotting Jacques , Osterheld Maria-Chiara , Di Bernardo Stefano
Published: October 2009

We describe a term newborn who, after a normal gestational course, presented at birth with absent cardiac activity and no spontaneous breathing. Death occurred within 30 h. Autopsy revealed placental villous immaturity, multiple acute hypoxic lesions, but also chronic hypoxic lesions like endocardial fibroelastosis. This striking association of endocardial fibroelastosis and placental villous immaturity is reviewed and correlated with 2 other cases of placental villous immaturity that led to in utero death at 39 and 41 weeks of gestation. Placental villous immaturity must be suspected and looked for by both pediatricians and obstetricians in every case of stillbirth or perinatal asphyxia of unclear origin. In order to minimize the risk of recurrence in further pregnancies, elective cesarean section may be considered.
Ultrasound Evaluation of the Amount of Wharton’s Jelly and the Umbilical Coiling Index
Authors: Kurita Minoru , Hasegawa Junichi , Mikoshiba Takao , Purwosunu Yuditiya , Matsuoka Ryu , Ichizuka Kiyotake , Sekizawa Akhiko , Okai Takashi
Published: October 2009

Objectives: To investigate the association between the amount of Wharton’s jelly (WJ) and the umbilical coiling index (UCI). Methods: The subjects included 140 pregnant women in the 2nd or 3rd trimester. The antenatal UCI was calculated as the reciprocal of the distance between a pair of coils. The sonographic cross-sectional areas of the cord, arteries and vein were measured. The WJ area was calculated by subtracting areas of the total vessels from the cord. Results: UCIs were significantly smaller and WJ areas were significantly greater in the 3rd trimester than in the 2nd trimester. No correlations were observed between the UCI and WJ area in both trimesters. Conclusion: There is a reduction of the UCI during pregnancy. No direct correlations were found between the amount of WJ and UCI.
Fournier’s Gangrene: A Monographic Urology Center Experience with Twenty Patients
Authors: Martínez-Rodríguez R. , Ponce de León J. , Caparrós J. , Villavicencio H.
Published: October 2009

Background: Fournier’s gangrene (FG) is a fatal synergistic infectious disease with necrotizing fasciitis of the perineum and abdominal wall along with the scrotum and penis in males and the vulva in females. The aim of this study was to share our experience in the management of this infectious disease. Methods: A retrospective chart review was performed in 20 patients with a diagnosis of FG between January 1991 and December 2007. Patient’s age, source and predisposing factors, microbiological findings, duration of hospital stay, treatment modalities, and outcome were analyzed. Results: The mean age of the patients was 53.9 ± 9.56 (range 23–71) years. The source of gangrene was urinary in 5 patients, perirectal in 5, cutaneous in 1, and unknown in 9 patients. The main predisposing factors included diabetes mellitus in 9 patients (45%) and immunosuppression in 5 patients (25%). The mean duration of hospital stay was 39 ± 10 (range 6–62) days. Although early intervention and intensive treatment were carried out, 4 patients died with an overall mortality of 20% as a result of septicemia complications. The mortality rate was higher in elderly patients and those with diabetes mellitus, but it was not statistically significant. Regarding the mortality rate, duration of symptoms, number of debridements, culture results and source of infection were not found to be significant factors. Conclusions: FG is still a severe disease. Management of this infectious entity must be aggressive. Despite the use of contemporary effective antibiotic treatment, aggressive debridements, and state-of-the-art intensive-care conditions, FG still has high mortality and morbidity rates.
Congenital Gastric Outlet Obstruction by Pyloric Membrane: Prenatal and Postnatal Diagnosis and Management
Authors: Frisova Veronika , Kavalcova Lucie , Kyncl Martin , Vlk Radovan , Kucera Alexandr , Rocek Miloslav
Published: October 2009

Congenital gastric outlet obstruction is a rare condition representing only 1% of all gastrointestinal atresias. Prenatal diagnosis is uncommon and mostly confined to the third trimester of cases presenting a combination of polyhydramnios with dilated stomach. We report a case of congenital gastric outlet obstruction by pyloric membrane which was diagnosed prenatally in the third trimester by sonography and magnetic resonance imaging. The anomaly appeared to be isolated, thus a favorable outcome was expected. A baby girl weighing 3,430 g was delivered spontaneously at 36 weeks. Postnatal imaging methods confirmed the presence of a congenital gastric obstruction. 21 h after delivery, the baby underwent laparotomy, at which time a malrotation and pyloric membrane were found and resolved. The postoperative course was uneventful and the baby was discharged at the age of 18 days and remains well at controls.
Inpatient Hemodialysis Initiation: Reasons, Risk Factors and Outcomes
Authors: Crews Deidra C. , Jaar Bernard G. , Plantinga Laura C. , Kassem Hania S. , Fink Nancy E. , Powe Neil R.
Published: October 2009

Background/Aims: Inpatient initiation of chronic hemodialysis is considered undesirable because of cost and possible harms of hospitalization. We examined the patient characteristics and outcomes associated with inpatient initiation. Methods: In a prospective cohort study of incident dialysis patients, the independent association of inpatient hemodialysis initiation with patient outcomes was assessed in multivariable analyses with adjustment for patient characteristics and propensity for inpatient initiation. Results: A total of 410 of 652 (63%) hemodialysis patients began as inpatients; uremia and volume overload were the most commonly documented reasons. Compared to outpatients, inpatients were more likely to be unmarried, report less social support, have multiple comorbidities and be referred to a nephrologist 4 months or less prior to initiation. Inpatient initiation was protective for subsequent all-cause hospitalization (incidence rate ratio (IRR) = 0.92, confidence interval (CI) 0.89–0.94); this was most pronounced among those who had the highest propensity for inpatient initiation (IRR = 0.66, CI 0.56–0.78), including those referred late to nephrology. Similar results were found for infectious hospitalization. Mortality [hazard ratio = 1.03, CI 0.82–1.30] and cardiovascular events were not significantly different for inpatients versus outpatients. Conclusion: Inpatient hemodialysis initiation has a protective association with hospitalization among those patients referred late to nephrology, with multiple comorbidities and/or little social support.
A Small Reduction in the Ankle-Brachial Index Is Associated with Increased Mortality in Patients on Chronic Hemodialysis
Authors: Kato Akihiko , Takita Takako , Furuhashi Mitsuyoshi , Kumagai Hiromichi , Hishida Akira
Published: October 2009

Background: High pulse wave velocity (PWV) and a low ankle-brachial index (ABI) are associated with mortality in hemodialysis (HD) patients. Recently, the cardio-ankle vascular index (CAVI) was developed as a novel index of arterial stiffness independent of blood pressure. Methods: We compared brachial-ankle PWV (baPWV), the ABI and the CAVI as predictors of mortality in 194 HD patients (age 64 ± 12 years; time on HD 111 ± 96 months) during a follow-up period of 39 ± 4 months (range 31–46). Results: The ABI was significantly positively correlated with serum albumin and negatively with log-transformed highly sensitive C-reactive protein (p < 0.01), while baPWV and the CAVI were not. Of 194 patients, 39 patients (20.1%) died during the follow-up, 25 (64.1%) of cardiovascular causes. Kaplan-Meier analysis revealed that the patients with an ABI in the lowest tertile (<1.0) had a significantly lower survival rate (p < 0.01). Cox hazards analysis after adjustment for the conventional risk factors revealed that an ABI value in the lowest tertile was a determinant of total mortality when compared with ABI values in the highest tertile [>1.1; hazard ratio 3.50 (95% confidence interval 1.20–10.20); p = 0.02]. In contrast, baPWV and the CAVI were not associated with mortality. Conclusion: These findings suggest that a small reduction in the ABI (<1.0) is an independent predictor of all-cause mortality in chronic HD patients.
Does Diabetes Mellitus Predispose to Increased Fluid Overload in Peritoneal Dialysis Patients?
Authors: Davenport Andrew , Willicombe Michelle Kay
Published: October 2009

Background: Diabetic peritoneal dialysis patients have been reported to have faster peritoneal solute transport and may be at risk of reduced ultrafiltration volumes, leading to fluid overload. Methods: We audited multi-frequency bioimpedance data from 198 consecutive peritoneal dialysis patients (141 nondiabetics and 57 diabetics). Results: Diabetic patients had increased body mass index (males 27 ± 4 vs. 26 ± 4; females 28 ± 5 vs. 25 ± 4; p < 0.01 for both), waist to hip ratio (males 0.94 ± 0.07 vs. 0.94 ± 0.04; females 0.99 ± 0.9 vs. 0.94 ± 0.09; p < 0.01 for both) and body fat (males 31 ± 8 vs. 26 ± 11%, p < 0.05; females 40 ± 8 vs. 33 ± 10%, p < 0.01) compared to nondiabetic patients. D4/P creatinine was greater for the female diabetic patients than the nondiabetic patients (0.75 ± 0.1 vs. 0.69 ± 0.1; p = 0.044); otherwise, the peritoneal equilibrium test (PET) results did not differ. Extracellular water (ECW) adjusted for height was similar in diabetic and nondiabetic patients, but the ratio of ECW to total body water (TBW) was greater for diabetics (males 0.40 ± 0.01 vs. 0.39 ± 0.01; females 0.39 ± 0.01 vs. 0.38 ± 0.01; p < 0.05 for both). Conclusions: Diabetic and nondiabetic patients had similar PET results, 24-hour net peritoneal ultrafiltration and blood pressure control. The ratio of ECW to TBW was greater in diabetic patients, and although this could be due to a loss of intracellular water, as albumin and C-reactive protein did not differ, it suggests that diabetic peritoneal dialysis patients have an expanded extracellular volume.
Evaluation of Oxidant-Antioxidant Balance in Patients on Maintenance Haemodialysis: A Comparative Study of Dialyzers Membranes
Authors: Macías Núñez Juan F. , Ghais Zoubiair , Bustamante Jesus , Lopez-Novoa Jose M.
Published: October 2009

Background: Haemodialysis (HD) exacerbates oxidative stress (OS). The polymethyl-methacrylate (PMMA)-BK-F membrane ameliorates OS and inflammation markers compared to polyacrylonitrile (PAN/AN69) and cellulose membranes. This may be due to the size of pore radius, high flux or other specific properties of PMMA membranes. Aim: To compare OS and inflammatory status in HD-treated end stage renal disease patients with membranes of different pore size radius and flux. Methods: 47 patients of both sexes were studied. The HD membranes with which the patients were normally treated were changed to BK-P or B-3 membranes for 6 months. Intracellular and extracellular components of the oxidant-antioxidant balance (OAB), C-reactive protein (CRP), β2-micro-globulin (β2µ-globulin), albumin and transferrin were measured. Results: A significant decrease in red cell membrane thiobarbituric acid reacting substances and an increase in cytosolic superoxide dismutase (SOD) and plasma total antioxidant substances were observed in all patients after 6 months of treatment with BK-P and B-3 membranes except SOD and CRP in patients previously dialysed with triacetate cellulose membranes. Albumin and transferrin remained unmodified. β2µ-globulin significantly decreased after treatment with PMMA membranes. Conclusion: BK-P and B-3 HD membranes improved the OAB, β2µ-globulin and CRP compared to PAN/AN69 and cellulose diacetate membranes.
Peripheral Cytokines and Chemokines in Alzheimer’s Disease
Authors: Lee Kang Soo , Chung Ji Hyung , Choi Tae Kyou , Suh Shin Young , Oh Byoung Hoon , Hong Chang Hyung
Published: October 2009

A chronic inflammatory process has been implicated in the neuropathology of Alzheimer’s disease (AD). The present review focuses on the current knowledge of circulating serum and plasma biomarkers of AD that are linked to inflammatory reactions. There is abundant evidence that inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Interleukins 1, 4, 6, 10, 12, 16, and 18, tumour necrosis factor, and several chemokines have been suggested as biomarkers of AD. Nonetheless, data on circulating cytokine levels are somewhat inconsistent with regard to peripheral cytokine dysregulation in AD. In summary, definite statements concerning differences in inflammatory biomarkers between controls and AD patients will require the use of sensitive multiplex assays in large patient groups in conjunction with measures of disease severity.
A Glimpse of Canaan, 40 Years On
Authors: Mohr J.P.
Published: October 2009

During the last few decades an explosion in definitions has occurred covering brief to permanent focal syndromes, diagnostic categories for stroke and subtypes, scoring systems characterizing clinical syndromes as well as imaging, and fostered the ascendancy of biostatistics and meta-analyses. These advances have led to the clinical trials which have changed the management, hyperacute therapy and prevention of recurrent stroke. Stroke trial design is now so well codified that its form is expected by the funding agencies, especially companies supporting trials. Despite criticism, transient ischemic attacks remain >24 h, uncommon diagnoses now fit into ‘stroke of other determined mechanism’, hyperacute treatment within 3, maybe 6 h is standard, as are outcomes at 30 days and 3 months. Unsettling to some, the randomized clinical trial may have reached a plateau in development. Clinical trials have also passed the point where outcomes can be measured in easily described events. The current problems find their focus in smaller cohorts, requiring multicenter efforts, nowadays spanning continents. They have also crossed into areas formerly considered the exclusive purview of sibling specialties, some members not predictably as concerned with the same research questions. Threats to the randomized clinical trial are also emerging in outcomes research. This approach is popular with agencies hoping to apply the widely accepted definitions to readily available clinical databases and will see only more use in times of limited budgets. One effect has been the unintentional restriction into the algorithms of new subtypes of ischemic and hemorrhagic stroke. Similarly, there has been insufficient focus on the effect of functional reorganization on poststroke clinical changes. It was long neglected when the clinical effects of lesions were inferred more or less permanent and explained as inferred ambidexterity, reversible tissue deactivation from edema and diaschisis. It was even explained that embolism was a transient process, leaving little brain injury in its wake. Long awaited, modern technologies are at last providing a means to study functional reorganization and compensatory mechanisms. Current results predict a radical change in our understanding of the course of syndromes from focal lesions, hopefully opening a new era for clinical neurology, maybe even a resurrection of semiology. Studies can be pursued in advance of lesions, during the poststroke course of living patients and for those planned for brain interventions, which could perturbate pretreatment functions and pathways. Those long dead would have envied us our current opportunity. Uncertain to be among those who reap the eventual harvest, this author is grateful for a glimpse of Canaan.
Cognitive Functioning Is Related to Physical Functioning in a Longitudinal Study of Women at Midlife
Authors: Ford Kathleen , Sowers MaryFran , Seeman Teresa E. , Greendale Gail A. , Sternfeld Barbara , Everson-Rose Susan A.
Published: October 2009

Background: Studies have reported declines with age in cognitive or physical functioning, but rarely identify whether these are parallel or linked events in the same study. Furthermore, most research in this area has focused on persons in late life rather than midlife. Objective: The objective of the study was to determine (1) if cognitive functioning was related to physical functioning and whether this relationship persisted after adjustment for age, menopause status, metabolic status, depression and socioeconomic resources, and (2) if changes in physical functioning were associated with changes in cognitive functioning over a 4-year follow-up period. Methods: Data were from the Study of Women’s Health Across the Nation (SWAN), a multi-site, longitudinal study of women aged 46–56 years at follow-up examination 4. Three follow-up examinations (study years 04, 06 and 08) included measures of physical functioning perception (MOS SF-36) and cognitive functioning [Symbol Digit Modality Test (SDMT), Digit Span Backward Test (DSBT), and East Boston Memory Test (EBMT)] (n = 2,405). Results: Women with lower cognitive functioning scores also had lower perceived physical functioning scores. While adjustment for covariates attenuated the association between perceived physical functioning and both the SDMT and EBMT cognitive measures, these associations remained statistically significant. Additionally, the 4-year change in perceived physical functioning was significantly associated with the 4-year change in the EBMT. Conclusions: At midlife, there were associated declines in cognitive and perceived physical functioning scores, commencing at midlife in women.
Coexistence of Pemphigus vulgaris, Malignant Melanoma and Low-Grade Lymphoma
Authors: Kyriakis K. , Stavropoulos P. , Hatziolou E. , Dellidis G. , Varelzidis A. , Tosca A.
Published: October 2009

A 53-year-old female patient with pemphigus vulgaris under continuous immunosuppressive therapy for about 2 years presented a superficial spreading malignant melanoma on a pre-existing melanocytic naevus. After surgical removal of the inguinal lymph node group, a diffuse low-grade polymorphous immunocytoma was proved both histologically and immunocytochemically. The possible induction mechanisms are discussed.
L-Tryptophan-Induced Eosinophilia-Myalgia Syndrome
Authors: Mainetti C. , Fathi M. , Saurat J.-H.
Published: October 2009

Abnormal metabolism of tryptophan is one of the possible aetiological factors in the L-tryptophan-induced eosinophilia-myalgia syndrome (EMS). We studied the plasma levels of tryptophan and serotonin and the urinary excretion of kynurenine and 5-hydroxyin-doleacetic acid after oral intake of L-tryptophan in 1 subject with EMS and 2 healthy subjects. The test was repeated with concomitant administration of pyridoxine. In the patient there were elevated levels of plasma tryptophan during the loading and increased elimination of kynurenine in the urine both during and after the L-tryptophan test. During pyridoxine administration tryptophan levels and kynurenine elimination were much reduced, and kynurenine elimination was similar to that of controls. This study (i) confirms that an abnormal metabolism of L-tryptophan occurs in EMS patients and (ii) shows that this can be corrected by pyridoxine.
Tumor of Follicular Infundibulum
Authors: Koch B. , Rufli T.
Published: October 2009

Tumor of the follicular infundibulum is a rare, benign proliferative follicular disorder. A case of multiple lesions in a 37-year-old woman is reported. The diagnosis was made histologically.
Primary Localized Cutaneous Nodular Amyloidosis: Case Report and Biochemical Analysis of Amyloid
Authors: Konohana A. , Teraki Y. , Tajima S. , Araki Y. , Kitamura K. , Nishikawa T.
Published: October 2009

We report a patient with scalp lesions of primary localized cutaneous nodular amyloidosis. The extensive examination revealed no systemic involvement. Analysis of glycosaminoglycans (GAGs) in amyloid deposits showed a twofold increase as compared with normal skin, which was due to the increase in dermatan sulfate. Local disorders of GAG metabolism may be related to the amyloid fibril formation. Amyloid fibrils were purified and identified electron-microscopically, which consisted of two major 12,000- and 13,000-dalton and minor 29,000- and 48,000-dalton peptides. Western blotting analysis showed a minor 29,000-dalton peptide reactive with antibodies against both κ and λ light chains of immunoglobulin. There is a possibility that some components of amyloid in some cases of primary localized cutaneous nodular amyloidosis may consist of both κ and λ immunoglobulin light chains.
Dermatomyositis and Pregnancy
Authors: Ishii N. , Ono H. , Kawaguchi T. , Nakajima H.
Published: October 2009

Dermatomyositis is a rare disease complicating pregnancy. We treated a patient in whom two pregnancies were complicated by dermatomyositis. In the first of the two gestations, a mild form of the disease arose in the last trimester. In the second gestation, the disease was inactive following treatment with 0.3 mg/kg/day prednisolone. Both the mother and two children have since been doing well.
Subcutaneous Leiomyosarcoma Developing in a Radiation Dermatitis
Authors: Yamamura T. , Takada A. , Higashiyama M. , Yoshikawa K.
Published: October 2009

A case of subcutaneous leiomyosarcoma developing in a skin affected by radiation dermatitis is presented. A 59-year-old patient had been suffering from radiation dermatitis induced by radiotherapy for a mediastinal tumor diagnosed at 24 years of age. Thirty-four years later, slow growing nodules developed in this lesion. Light and electron microscopic studies revealed that the tumor was a subcutaneous leiomyosarcoma. There is no previous report of a subcutaneous leiomyosarcoma developing in radiation dermatitis.
Noninvasive Procedures in Dermatology
Authors: Wolf R. , Brenner S.
Published: October 2009

Although in the area of incisional surgery the level of sterile techniques has improved in recent years and approaches that of the surgical standards in other specialties, one cannot say the same with regard to some of the nonsurgical or semisurgical procedures. Here, unfortunately, there are even no standards to aim for and no guidelines to adopt. Since in the field of nonsurgical cosmetic skin care dermatologists have a unique position we alone must shoulder the responsibility for setting the standards and determining the appropriate conditions for carrying out these procedures. Unfortunately, it appears that in certain of the dermatologic procedures not involving actual skin incision, the level of sterility has not improved for decades. In such dermatologic procedures there are marked discrepancies between the care taken to maintain a high degree of sterility of instruments that penetrate the skin, compared with the lack of attention to sterility of instruments that do not directly penetrate the skin and the area surrounding the procedure site. It seems that the guiding principle we must strive for is to prevent the transmission of infection from one patient to another. The emphasis should be not on sterility per se but on the prevention of transmission of disease from patient to patient.
Bullous Pemphigoid Antigen Expression in Pam 212 Cells Induced by the Addition of Platelet Activating Factor
Authors: Karashima T. , Okubo K. , Hachisuka H. , Sasai Y.
Published: October 2009

Platelet activating factor (Paf-acether) is a phospholipid which has various activities including platelet and neutrophil aggregation and eosinophil chemotaxis. We have previously reported that the blister fluids of bullous pemphigoid possess platelet aggregation activity and suggested that Paf-acether might be concerned with the accumulation and activation of neutrophils and eosinophils. In this study, we examined the influence of Paf-acether on BP antigen expression on Pam 212 cells. Paf-acether enhanced the expression of BP antigen on Pam 212 cells and this expression was blocked by Paf-acether antagonist. Our observations might suggest that Paf-acether contributes to the blister formation not only by the activation of inflammatory cells but the enhancement of BP antigen.
Treatment of Inflammatory Linear Verrucous Epidermal Nevus
Authors: Rulo H.F.C. , van de Kerkhof P.C.M.
Published: October 2009

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare and chronic skin disorder, which may trouble the patient considerably. The condition is generally believed to be resistant to therapy, although some authors have reported success with several treatments, including dithranol and etretinate. The present case, a classical presentation of ILVEN, again illustrates the refractoriness to various treatments, including an experimental treatment with topical 13-cis-retinoic acid. A review of the literature on therapeutic possibilities of ILVEN is presented. Based on our own observations and literature data, it is attractive to hypothesize that a positive result with treatments such as dithranol and retinoids should be interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.
Acute Generalized Exanthematic Pustulosis
Authors: Bernard P. , Bedane C. , Catanzano G. , Robbe J. , Bonnetblanc J.M.
Published: October 2009

A 74-year-old woman developed a generalized pustular dermatosis with erythema-multiforme-like and vesiculobullous lesions 10 days after beginning a treatment by nadoxolol. Despite the clinical polymorphism of the eruption, histology constantly revealed the presence of subcorneal pustules, even within the epidermis overlying subepidermal bullae. The eruption spontaneously healed after discontinuation of nadoxolol.
Hair Casts
Authors: Van Staey A. , Suys E. , Derumeaux L. , De Raeve L. , De Coninck A. , Roseeuw D.
Published: October 2009

Hair casts are small cylindrical structures, encircling individual scalp hairs but easily movable along the involved hair shafts. This hair disorder of unknown pathogenesis is only rarely mentioned in the dermatologic literature. We report the case of a 5-year-old girl, who has been treated during 2 years for pediculosis capitis. The literature about hair casts is reviewed.
Lyme Borreliosis
Authors: Schmidli J. , Meyer J.
Published: October 2009

Borrelia burgdorferi, the etiologic agent of Lyme disease, was the topic of an international conference in Stockholm which assembled 500 scientists from all over the world. About 300 oral and poster presentations revealed many new details on the complex life history of this bacterium, its molecular characteristics, the clinical consequences of human and animal infections, new diagnostic procedures and therapeutic regimens.
The Immunogold-Silver Staining Procedure in the Study of Freshly Suspended Langerhans Cells at the Transmission Electron Microscopic Level
Authors: Manara G.C. , Ferrari C. , Torresani C. , De Panfilis G.
Published: October 2009

The potential of an immunogold-silver staining for the study of human suspended Langerhans cells at the transmission electron microscopic level was evaluated. Cells were labeled, by using a preembedding technique, with 5-nm colloidal gold particles followed by silver enhancement. The use of small colloidal gold particles permits a detection of small quantities of antigen; the metallic silver deposition around gold granules gives rise to a large electron-dense marker which can be easily detected even at low magnification. Ultrastructural details were well preserved, and the background was not significant. The major advantage of the present immunogold-silver staining is that it enables to detect labeled cells easily, even when limited amounts of antigenic moieties are present on a low percentage of cells. Therefore, a rapid and simultaneous evaluation of both immunophenotype and ultrastructural details of investigated cells is allowed.
Follicular Impetigo as Presenting Sign of Systemic Lupus erythematosus
Authors: Lazzari T. , Parodi A. , Rebora A.
Published: October 2009

A patient with an unusual form of follicular impetigo, who later developed classical systemic lupus erythematosus (SLE) is described. When she had pyoderma, direct immunofluorescence and serology already suggested a connective tissue disease. Pyoderma could have been the presenting manifestation of SLE.