bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer
Authors: Zhang Qing , Bhola Neil E. , Lui Vivian Wai Yan , Siwak Doris R. , Thomas Sufi M. , Gubish Christopher T. , Siegfried Jill M. , Mills Gordon B. , Shin Dong , Grandis Jennifer Rubin
Published: April 2007

Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) aurocrine regulatory pathway in HNSCC, where GRP stimulates Src-dependent cleavage of EGFR proligands with subsequent EGFR phosphorylation and mitogen-activated protein kinase (MAPK) activation. To determine whether GRPR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a GRPR antagonist (PD176252) in conjunction with an EGFR tyrosine kinase inhibitor (erlotinib). Combined blockade of GRPR and EGFR pathways significantly inhibited HNSCC, but not immortalized mucosal epithelial cell, proliferation, invasion, and colony formation. In addition, the percentage of apoptotic cells increased upon combined inhibition. The enhanced antitumor efficacy was accompanied by increased expression of cleaved poly(ADP-ribose) polymerase (PARP) and decreased phospho-EGFR, phospho-MAPK, and proliferating cell nuclear antigen (PCNA). Using reverse-phase protein microarray (RPPA), we further detected decreased expression of phospho–c-Jun, phospho-p70S6K, and phospho-p38 with combined targeting. Cumulatively, these results suggest that GRPR targeting can enhance the antitumor effects of EGFR inhibitors in head and neck cancer. [Mol Cancer Ther 2007;6(4):1414–24]
Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function
Authors: Schafer-Hales Katherine , Iaconelli Jon , Snyder James P. , Prussia Andrew , Nettles James H. , El-Naggar Adel , Khuri Fadlo R. , Giannakakou Paraskevi , Marcus Adam I.
Published: April 2007

Farnesyl transferase inhibitors (FTI) exhibit anticancer activity as a single agent in preclinical studies and show promise in combination with other therapeutics in clinical trials. Previous studies show that FTIs arrest cancer cells in mitosis; however, the mechanism by which this occurs is unclear. Here, we observed that treatment of various cancer cell lines with the FTI lonafarnib caused mitotic chromosomal alignment defects, leaving cells in a pseudometaphase state, whereby both aligned chromosomes and chromosomes juxtaposed to the spindle poles (termed “lagging chromosomes”) were observed in the same cell. To determine how this occurs, we investigated the functionality of two farnesylated mitotic proteins, CENP-E and CENP-F, which mediate chromosomal capture and alignment. The data show that lonafarnib in proliferating cancer cells depletes CENP-E and CENP-F from metaphase but not prometaphase kinetochores. Loss of CENP-E and CENP-F metaphase localization triggered aberrant chromosomal maintenance, causing aligned chromosomes to be prematurely released from the spindle equator and become lagging chromosomes, resulting in a mitotic delay. Furthermore, lonafarnib treatment reduces sister kinetochore tension and activates the BubR1 spindle checkpoint, suggesting that farnesylation of CENP-E and CENP-F is critical for their functionality in maintaining kinetochore-microtubule interactions. Importantly, apparently similar chromosomal alignment defects were observed in head and neck tumors samples from a phase I trial with lonafarnib, providing support that lonafarnib disrupts chromosomal maintenance in human cancers. Lastly, to examine how farnesylation could regulate CENP-E in mediating kinetochore-microtubule attachments, we examined possible docking motifs of a farnesyl group on the outer surface of the microtubule. This analysis revealed three hydrophobic patches on the tubulin dimer for insertion of a farnesyl group, alluding to the possibility of an association between a farnesyl group and the microtubule. [Mol Cancer Ther 2007;6(4):1317–28]
Levels of p27kip1 determine Aplidin sensitivity
Authors: Moneo Victoria , Serelde Beatriz G. , Leal Juan F.M. , Blanco-Aparicio Carmen , Diaz-Uriarte Ramon , Aracil Miguel , Tercero Juan C. , Jimeno José , Carnero Amancio
Published: April 2007

Aplidin (plitidepsin) is a novel anticancer drug isolated from the marine tunicate Aplidium albicans. Aplidin shows potent antitumor activity in preclinical models against a wide variety of human tumors. Aplidin is currently in phase II clinical trials in a variety of solid tumors and hematologic malignancies. Moreover, clinical studies of Aplidin in combination with other agents are ongoing because it generally lacks cross-resistance with other known cytotoxic drugs. The mode of action of Aplidin in tumor cells is only partially understood. Aplidin induces an early oxidative stress response, which results in a rapid and sustained activation of the epidermal growth factor receptor, the nonreceptor protein tyrosine kinase Src, and the serine threonine kinases c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase. Here, we show that sensitivity to Aplidin correlates inversely with the levels of expression of the cyclin-dependent kinase inhibitor p27kip1 (p27) in a panel of low passaged human sarcoma cell lines. Aplidin induces p27 through an oxidation-dependent mechanism and the reduction of p27 levels by specific short hairpin RNA increases Aplidin sensitivity. We confirmed these results in p27 null mouse embryonic fibroblasts corroborating the specificity of the p27 role in Aplidin response because p21waf1 null mouse embryonic fibroblasts do not show this increased sensitivity. We propose a mechanism of action of Aplidin involving p27 and support the analysis of p27 in the response to Aplidin in currently ongoing clinical trials to establish the levels of this protein as response predictor. [Mol Cancer Ther 2007;6(4):1310–6]
Real-Time Neuronavigation with High-Quality 3D Ultrasound SonoWand® in Pediatric Neurosurgery
Authors: Roth Jonathan , Biyani Naresh , Beni-Adani Liana , Constantini Shlomi
Published: April 2007

Intraoperative ultrasound (IOUS) serves as a basic imaging tool in neurosurgery. However, its low quality and difficulty in interpreting the images make its use as a resection control tool and navigation system cumbersome. We present our experience using a high-resolution 3D IOUS system combined with a navigation system in pediatric cranial surgery. We retrospectively reviewed 16 pediatric neurosurgical procedures in which a high-resolution 3D IOUS combined with a navigation system was used. The system enables basic navigation based on preoperative computed tomography or magnetic resonance imaging scans. In addition, IOUS images serve as a data set for updated intraoperative navigation. The indications for IOUS were preoperative navigation to define the skin incision and exact craniotomy site, and for real-time neuronavigation and resection control during tumor removal. The added time per case was short and no technical difficulties were encountered. High-resolution 3D IOUS combined with navigation systems has advantages for the pediatric neurosurgical population, including both real-time basic navigation and improved resection control.
Corpus Callosotomy for Treatment of Pediatric Epilepsy in the Modern Era
Authors: Rahimi Scott Y. , Park Yong D. , Witcher Mark R. , Lee Ki H. , Marrufo Manuel , Lee Mark R.
Published: April 2007

Objective: The purpose of this study was to evaluate seizure outcome in children with intractable secondary generalized epilepsy without a resectable focus who underwent complete corpus callosotomy and compare these results to those of anterior two-third callosotomy. Method: Data were obtained for all patients who underwent a corpus callosotomy from 2000 to 2005. The study involved 37 patients. Eleven patients had anterior two-third corpus callosotomy compared with 28patients who underwent complete corpus callosotomy. Two of these patients had completion of their callosotomy following initial partial callosotomy. Seizure type, seizure frequency, and family satisfaction were evaluated for all patients pre- and postoperatively. Results: A reduction of ≧75% in seizures occurred in 75% of the total-callosotomy patients compared to 55% of the partial-callosotomy patients. Family satisfaction for complete and partial callosotomy was 89 and 73%, respectively. No prolonged neurologic deficits were observed in either group. Conclusion: Complete corpus callosotomy is the most effective treatment for secondary generalized intractable seizures not amenable to focal resection in children.
Tethered Cord Syndrome: An Updated Review
Authors: Lew Sean M. , Kothbauer Karl F.
Published: April 2007

Tethered cord syndrome (TCS) is a diverse clinical entity characterized by symptoms and signs which are caused by excessive tension on the spinal cord. The majority of cases are related to spinal dysraphism. TCS can present in any age group, and presentations differ according to the underlying pathologic condition and age, with pain, cutaneous signs, orthopedic deformities and neurological deficits being the most common. Surgical untethering is indicated in patients with progressive or new onset symptomatology attributable to TCS. The surgical strategy aims to release the tethering structure and thus the chronic tension on the cord. Early operative intervention is associated with improved outcomes. Pain relief is accomplished in almost all cases. Realistic surgical goals include relief of pain and stabilization of neurological function, although improvement in function is often seen. Cord untethering can also halt the progression of scoliosis. The benefits of surgery are debated in asymptomatic patients and patients with normal imaging.
Foraging Habits of Alouatta palliata mexicana in Three Forest Fragments
Authors: Asensio Norberto , Cristobal-Azkarate Jurgi , Dias Pedro Américo D. , Vea Joaquim J. , Rodríguez-Luna Ernesto
Published: April 2007

The activity patterns and diet of howler monkeys(Alouatta palliata mexicana)were studied in 3 forest fragments in south-eastern Mexico: Playa Escondida (PLA), Agaltepec Island (AGA) and Arroyo Liza (LIZ). Intersite differences offered the opportunity to investigate the foraging adaptations of howler monkeys in response to population and habitat size. In the largest fragment (PLA), the howlers’ diet was based on high-quality items (fruit and young leaves). In AGA, where the density of howlers was the highest, their diet was mostly folivorous with a marked exploitation of uncommon food items such as vines, lianas, shrubs and herbs. The dietary differences in AGA were accompanied by more time spent travelling and less time spent resting. Although LIZ was the smallest fragment and had a high howler density, the small group size and the use of energy-minimizing strategies (less time spent travelling and more time spent resting) probably allowed howlers to maintain a frugivorous diet.
Detection of Approximal Caries by Clinical and Radiographic Examination in 9-Year-Old Swedish Children
Authors: Lillehagen M. , Grindefjord M. , Mejàre I.
Published: April 2007

The aims were to determine caries prevalence in 9-year-olds belonging to a low-caries prevalence population and to assess how accurately some commonly used risk factors/risk markers (predictors) can identify additional approximal caries as judged from bitewing examination (BW). One calibrated dentist examined 117 consecutive 9-year-olds from the inner city of Stockholm. The predictors were the number of clinically detected dfs and DFS, visible plaque, salivary mutans streptococci, tooth brushing habits, consumption of sugary products, parents’ education, and (before BW) an overall clinical judgement by the examiner. Analyses of the data included sensitivity and specificity and a multiple logistic regression model. When BW was included, the mean DFS was 0.27 and the mean dfs 1.74. For approximal enamel and dentin lesions, the average gain from BW was 0.20 lesions for permanent first molars and 1.23 lesions for primary molars. Altogether, 48% of the children benefited from BW. The best predictors of additional approximal caries from BW were presence of caries (cavitation/dentin level) on occlusal surfaces of permanent first molars and the dentist’s judgement based on clinical findings, both with a combined sensitivity and specificity of 134%. The only statistically significant variables in a logistic regression model were the dentist’s judgement and the child’s statement about regular tooth brushing. It is concluded that a sizeable proportion of 9-year-olds, representing a low-caries prevalence population, benefited from BW. However, the ability to identify these children from the predictors was limited.
Long-Term Effect of Xylitol Gum Use on Mutans Streptococci in Adults
Authors: Haresaku S. , Hanioka T. , Tsutsui A. , Yamamoto M. , Chou T. , Gunjishima Y.
Published: April 2007

Many studies have shown the effects of chewing xylitol gum on mutans streptococci (MS) over short- and long-term periods in children; however, few studies have addressed long-term periods in adults. The objective of this investigation was to examine for 6 months the effects of chewing xylitol gum on MS in saliva and plaque in 127 adults (mean age 28.0 years). The participants were assigned to three groups according to gum type, in part taking preference for flavor into account and in part at random: xylitol (XYL), maltitol (MAL) and control (CR); 33, 34 and 27 subjects in each group, respectively, completed the trial. Daily gum use of the XYL and MAL groups was 7.9 and 7.1 g, respectively. MS levels, which declined significantly in saliva (p < 0.05) and plaque (p < 0.001) in the XYL group after 6 months, exhibited a significant increase in plaque in the MAL group (p < 0.001). Differences in relative changes of MS levels in plaque during the experimental period were significant between the XYL group and the CR (p < 0.05) and MAL groups (p < 0.001). Differences in relative change of amount of plaque during the experimental period were not statistically significant between the groups. The present study demonstrated that chewing xylitol gum for 6 months continued to inhibit the growth of mutans streptococci in adults.
Ultrasonic Determination of the Effect of Casein Phosphopeptide-Amorphous Calcium Phosphate Paste on the Demineralization of Bovine Dentin
Authors: Yamaguchi K. , Miyazaki M. , Takamizawa T. , Inage H. , Kurokawa H.
Published: April 2007

The purpose of this study was to investigate the demineralization of dentin by measuring changes in the velocity of the sonic longitudinal waves transmitted through this substrate. One group of samples was immersed in demineralization solution for 10 min twice a day and then stored in artificial saliva. Two additional groups of samples were treated with a solution of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste or a placebo paste without CPP-ACP before demineralization and a control group was stored in artificial saliva. The sonic velocity of the demineralized specimens was found to decrease significantly over time. No significant increase in sonic velocity was observed in specimens treated with CPP-ACP, suggesting that CPP-ACP acted to prevent demineralization.
Effect of White Cheese and Sugarless Yoghurt on Dental Plaque Acidogenicity
Authors: Şaroğlu Sönmez I. , Aras Ş.
Published: April 2007

White cheese and sugarless yoghurt are frequently consumed traditional Turkish foods. The aim of this study was to assess their acidogenic potential when eaten alone or following a rinse with sucrose solution. Plaque pH was measured by a pH microelectrode at baseline to determine the resting plaque pH and at time intervals of 1–60 min after rinsing with 10% sucrose solution or eating the test food for 1 min. White cheese consumption for 1 min increased the plaque pH. When white cheese was eaten 5 min after rinsing with 10% sucrose solution, the plaque pH rose rapidly. After sugarless yoghurt consumption, the pH fell to a similar minimum as for sucrose after 5 min but returned to baseline levels after 30 instead of 60 min. Consumption of sugarless yoghurt after a sucrose rinse initially reduced the plaque pH further but did not affect the time taken for pH to regain baseline levels.
Saliva-Promoted Adhesion of Streptococcus mutans MT8148 Associates with Dental Plaque and Caries Experience
Authors: Shimotoyodome A. , Kobayashi H. , Tokimitsu I. , Hase T. , Inoue T. , Matsukubo T. , Takaesu Y.
Published: April 2007

Colonization of enamel surfaces by Streptococcus mutans is thought to be initiated by the attachment of bacteria to a saliva-derived conditioning film (acquired pellicle). However, the clinical relevance of the contribution of saliva-promoted S. mutans adhesion in biofilm formation has not yet been fully elucidated. The aim of this study was to correlate saliva-promoted S. mutans adhesion with biofilm formation in humans. We correlated all measurements of salivary factors and dental plaque formation in 70 healthy subjects. Dental plaque development after thorough professional teeth cleaning correlated positively with S. mutans adhesion onto saliva-coated hydroxyapatite pellets and the glycoprotein content of either parotid or whole saliva. Saliva-promoted S. mutans adhesion and glycoprotein content were also positively correlated with each other in parotid and whole saliva. By contrast, neither salivary mutans streptococci, Lactobacillus nor Candida correlated with biofilm formation. Parotid saliva-mediated S. mutans adhesion was significantly higher in 12 caries-experienced (CE) subjects than in 9 caries-inexperienced (CI) subjects. Salivary S. mutans adhesion was significantly less (p < 0.01) in the CI group than in the CE group. In conclusion, the present findings suggest the initial S. mutans adhesion, modulated by salivary protein adsorption onto the enamel surface, as a possible correlate of susceptibility to dental plaque and caries.
The Influence of Fluoride Varnish on the Attrition of Dentine
Authors: Li H. , Watson T.F. , Sherriff M. , Curtis R. , Bartlett D.W.
Published: April 2007

Previous investigations have shown the potential for fluoride to be protective in an abrasion/erosion laboratory model. The aim of this study was to investigate the effect of high concentrations of fluoride delivered in a varnish on attrition of dentine. Fifteen caries-free, intact lower third molar teeth were sectioned and the enamel removed by a water-cooled diamond disc. Polished dentine surfaces were divided into 8 areas, 4 of which were randomly covered with a high-concentration fluoride varnish for 24 h. The samples were subjected to 5,000 cycles of attrition bathed under artificial saliva. Microhardness testing adjacent to the wear scars showed no statistical difference between the fluoride-treated (71.42 KHN, SD 10.52) and control surfaces (72.66 KHN, SD 9.69). The volume of the wear scar was statistically greater for the fluoride-treated surface at 9.6 µm3 (SD 4.92) and 8.13 µm3 (SD 5.54) for the control areas (p = 0.029). The low pH of the fluoride varnish appears to have increased the amount of wear from attrition in this laboratory study.
Surface Layer Erosion of Natural Caries Lesions with Phosphoric and Hydrochloric Acid Gels in Preparation for Resin Infiltration
Authors: Meyer-Lueckel H. , Paris S. , Kielbassa A.M.
Published: April 2007

The infiltration of proximal enamel lesions with low-viscosity light curing resins could be a viable approach to stop lesion progression. However, penetration of sealant might be hampered by the comparatively highly mineralized surface layers of natural lesions. Therefore, the aim of this study was to compare the efficacy of three different etching gels in removing the surface layer in various etching times. Extracted human molars and premolars showing proximal white spot lesions were cut across the demineralized areas. Ninety-six lesions expected from visual examination to be confined to the outer enamel (C1) were selected. The cut surface and half of each lesion were varnished, thus serving as control. Subsequently, the lesions were etched with either phosphoric (37%) or hydrochloric (5 or 15%) acid gel for 30–120 s (n = 8/group). Specimens were examined using confocal microscopy and transversal microradiography. Surface layer reduction was significantly increased in lesions etched with 15% HCl gel for 90 and 120 s compared to those etched with H3PO4 gel for 30–120 s (p < 0.05). No significant differences regarding the depths of erosion in the lesions compared to sound enamel could be observed (p > 0.05). An effective reduction in the surface layer of natural enamel caries can be achieved by etching with 15% hydrochloric acid gel for 90–120 s.
Detection of Proximal Caries in vitro Using Standard and Task-Specific Enhanced Images from a Storage Phosphor Plate System
Authors: Li G. , Sanderink G.C.H. , Berkhout W.E.R. , Syriopoulos K. , van der Stelt P.F.
Published: April 2007

Eight dentists evaluated 72 proximal surfaces of premolars with respect to all caries lesions and to lesions into dentine in digital images from a storage phosphor plate system. The images were processed in four different ways: (1) the default algorithm of the standard imaging system (DF); (2) an algorithm correcting for attenuation and visual response (AV), and two proprietary caries-specific enhancement algorithms (3) K1, and (4) K2, respectively. The lesions were validated by histological examination. There were no significant differences in the areas under the receiver operating characteristic curves between differently processed radiographs for the categories of all caries lesions and caries into dentine.
The Effect of Saliva on the Formation of KOH-Soluble Fluoride after Topical Application of Amine Fluoride Solutions of Varying Fluoride Concentration and pH
Authors: Rošin-Grget K. , Šutej I. , Linčir I.
Published: April 2007

The effect of saliva on the amount of KOH-soluble fluoride formed on a sound enamelsurface after application of amine fluoride solution of varying fluoride concentrations (1, 0.5 and 0.25% F) and pH (5.3, 4.5 and 4.0) was examined in an in vitro study. The saliva pretreatment increased the amount of KOH-soluble fluoride at the highest pH value. For any given fluoride concentration, the presence of saliva did not influence the amount of KOH-soluble fluoride. These data suggest that saliva could enhance the amount of KOH-soluble fluoride if the topical fluoride preparations are not highly acid.
Lack of Effect of Prior Treatment with Fluoride on Genotoxicity of Two Chemical Agents in vitro
Authors: Ribeiro D.A. , Marques M.E.A. , Salvadori D.M.F.
Published: April 2007

The goal of this study was to investigate the ability of fluoride to modulate the genotoxic effects induced by the oxidative agent hydrogen peroxide (H2O2) and the alkylating agent methyl methanesulfonate (MMS) in vitro by the single-cell gel (comet) assay. Chinese hamster ovary cells were exposed in culture for 1 h at 37°C to sodium fluoride at 7–100 µg/ml. NaF-treated and control cells were then incubated with 0–10 µM MMS in phosphate-buffered saline (PBS) for 15 min at 37°C, or 0–100 µM H2O2 in distilled water for 5 min on ice. Negative control cells were treated with PBS for 1 h at 37°C. Clear concentration-related effects were observed for the two genotoxins. Increase of DNA damage induced by either MMS or H2O2 was not significantly altered by pretreatment with NaF. The data indicate that NaF does not modulate alkylation-induced genotoxicity or oxidative DNA damage as measured by the single-cell gel (comet) assay.
Isolation and Characterization of a Population of Immature Dental Pulp Stem Cells Expressing OCT-4 and Other Embryonic Stem Cell Markers
Authors: Kerkis Irina , Kerkis Alexandre , Dozortsev Dmitri , Stukart-Parsons Gaëlle Chopin , Gomes Massironi Sílvia Maria , Pereira Lygia V. , Caplan Arnold I. , Cerruti Humberto F.
Published: April 2007

We report the isolation of a population of immature dental pulp stem cells (IDPSC), which express embryonic stem cell markers Oct-4, Nanog, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81 as well as several other mesenchymal stem cell markers during at least 25 passages while maintaining the normal karyotype and the rate of expansion characteristic of stem cells. The expression of these markers was maintained in subclones obtained from these cells. Moreover, in vitrothese cells can be induced to undergo uniform differentiation into smooth and skeletal muscles, neurons, cartilage, and bone under chemically defined culture conditions. After in vivo transplantation of these cells into immunocompromised mice, they showed dense engraftment in various tissues. The relative ease of recovery and the expression profiles of various markers justify further exploration of IDPSC for clinical therapy.
Anatomical Definition of the Subglottic Region
Authors: Kutta Hannes , Steven Philipp , Paulsen Friedrich
Published: April 2007

Background: Due to laryngeal neoplasia, as well as infectious and autoimmune diseases, the subglottic region is of great clinical relevance. However, descriptions of the subglottic structures are inconsistent. The aim of our study was to present a precise analysis of the subglottic region and derive functional and clinical conclusions. Methods: Histological, histochemical and immunohistochemical investigations as well as scanning electron microscopy were performed and combined with injection techniques applied to the subglottic region of the larynges of 33 body donors. Results: The three-dimensional extensions of the subglottic region were newly defined: the inferior arcuate line of the vocal cord was defined as the cranial border. The lower margin of the cricoid is the caudal border. Craniolaterally, the elastic cone and, further caudally, the cricoid form the border. Therefore, the definition presented comprises heretofore unnamed ventral and dorsal parts of the lower larynx. The subglottic region can be described as cylindrical, becoming smaller in the cranial direction, following the elastic cone. The ventral boundary is formed by the median part of the cricothyroid ligament (ligamentum conicum), the dorsal part by the cricoid cartilage. The walls of the subglottis are divided into three or four layers composed of collagenous and elastic fibres in which seromucous glands are embedded. Subglottic blood vessels including a tight subepithelial capillary plexus were delineated. Conclusion: The new definition of the subglottic extensions presented is helpful and essential for precise laryngeal tumour classification. The results indicate that the boundaries are unlikely to counteract tumour progression in the subglottis. Furthermore, the findings suggest that these structures contribute to temperature regulation of breath, protection against inflammation as well as breath frequency and depth-dependent mucus secretion.
How Does Our Brain Constitute Defense Mechanisms? First-Person Neuroscience and Psychoanalysis
Authors: Northoff Georg , Bermpohl Felix , Schoeneich Frank , Boeker Heinz
Published: April 2007

Current progress in the cognitive and affective neurosciences is constantly influencing the development of psychoanalytic theory and practice. However, despite the emerging dialogue between neuroscience and psychoanalysis, the neuronal processes underlying psychoanalytic constructs such as defense mechanisms remain unclear. One of the main problems in investigating the psychodynamic-neuronal relationship consists in systematically linking the individual contents of first-person subjective experience to third-person observation of neuronal states. We therefore introduced an appropriate methodological strategy, ‘first-person neuroscience’, which aims at developing methods for systematically linking first- and third-person data. The utility of first-person neuroscience can be demonstrated by the example of the defense mechanism of sensorimotor regression as paradigmatically observed in catatonia. Combined psychodynamic and imaging studies suggest that sensorimotor regression might be associated with dysfunction in the neural network including the orbitofrontal, the medial prefrontal and the premotor cortices. In general sensorimotor regression and other defense mechanisms are psychoanalytic constructs that are hypothesized to be complex emotional-cognitive constellations. In this paper we suggest that specific functional mechanisms which integrate neuronal activity across several brain regions (i.e. neuronal integration) are the physiological substrates of defense mechanisms. We conclude that first-person neuroscience could be an appropriate methodological strategy for opening the door to a better understanding of the neuronal processes of defense mechanisms and their modulation in psychoanalytic psychotherapy.
Assessing Alexithymia and Type A Behavior in Coronary Heart Disease Patients: A Multimethod Approach
Authors: Beresnevaité Margarita , Taylor Graeme J. , Bagby R. Michael
Published: April 2007

Background: Despite increasing emphasis on using multiple methods to assess personality constructs in psychosomatic research, previous investigations of relations between alexithymia and type A behavior (TAB) have been limited by the use of single methods of measurement and almost no attempt to assess subcomponents of TAB. The aims of this study were to (1) evaluate levels of agreement between structured interview assessments of alexithymia, TAB, hostility, and time urgency and well-established self-report measures of these constructs, and (2) explore relations between alexithymia and TAB and its subcomponents in patients with coronary heart disease (CHD). Methods: 62 CHD patients were investigated 6 weeks after coronary angioplasty. Alexithymia was assessed with the Diagnostic Criteria for Psychosomatic Research (DCPR) and the 20-item Toronto Alexithymia Scale (TAS-20). TAB was assessed with the DCPR and the Short Form of the Jenkins Activity Survey Type A scale (JAS-SF). Time urgency was assessed with the DCPR and the Speed/Impatience scale of the Jenkins Activity Survey (JAS-S), and hostility was assessed with the DCPR and the Hostility subscale of the Revised Symptom Checklist-90 (SCL-HOS). Results: The DCPR classifications showed reasonably high levels of agreement with the TAS-20 and JAS-SF classifications of alexithymia and TAB, but lower levels of agreement in identifying patients with high hostility on the SCL-HOS and high time urgency on the JAS-S. Alexithymia measured by both the DCPR and the TAS-20 was unrelated to both self-report and structured interview measures of TAB, hostility, and time urgency. Conclusions: The DCPR is a suitable screening instrument for assessing alexithymia and TAB, although the two constructs are unrelated.
Helper Function of the Wolffian Ducts and Role of Androgens in the Development of the Vagina
Authors: Drews U.
Published: April 2007

The development of a vagina as a separate outlet of the birth canal evolves at the transition of egg laying species to eutherian mammals. The derivation of the vagina from the Wolffian and Müllerian ducts and the contribution of the urogenital sinus are still open questions. Here experiments with the complete androgen receptor defect in the testicular feminisation (Tfm) mouse are reported which show that the vagina is formed by caudal migration of Wolffian and Müllerian ducts. The cranial ends of the Wolffian ducts successively regress while the Müllerian ducts fuse to form the vagina. Immunohistochemistry of the androgen receptor reveals that the caudal ends of the Wolffian ducts remain in the indifferent stage and therefore have been mistaken as sinuvaginal bulbs. The Wolffian ducts do not contribute to the vagina itself but have a helper function during downward movement of the vaginal bud in the female. In the male the caudal ends serve as androgen operated switch for the negative control of vaginal development. The results indicate that the rudimentary vagina in the complete androgen insensitivity syndrome (CAIS) corresponds to non obliterated caudal ends of the Müllerian ducts. Selective atresia of the vagina in the MRKH (Mayer-Rokitansky-Küster-Hauser) syndrome may be explained by the failure of Wolffian and Müllerian ducts to descend caudally.
The Neural Crest: Understanding Stem Cell Function in Development and Disease
Authors: Fuchs Sebastian , Sommer Lukas
Published: April 2007

Complex organs like the nervous system are composed of different cell types which are all derived from multipotent stem cells. In vertebrates, a transient population of stem cells, the neural crest, generates the entire peripheral nervous system as well as non-neural progeny. The developmental processes of cellular differentiation and proliferation require precise coordination and control. Errors in the programs that regulate stem cell function can lead to defects that manifest in developmental disorders, in some cases they might even induce cancer. It is therefore of fundamental interest to understand the mechanisms of stem cell maintenance and differentiation. Using the neural crest as a model system helps us not only to understand the role of stem cells in development but might also lead to new aspects for the cure of stem cell-related diseases.
New Technologies and Concepts for Rehabilitation in the Acute Phase of Stroke: A Collaborative Matrix
Authors: Siekierka E.M. , Eng K. , Bassetti C. , Blickenstorfer A. , Cameirao M.S. , Dietz V. , Duff A. , Erol F. , Ettlin T. , Hermann D.M. , Keller T. , Keisker B. , Kesselring J. , Kleiser R. , Kollias S. , Kool J.P. , Kurre A. , Mangold S. , Nef T. , Pyk P. , Riener R. , Schuster C. , Tosi F. , Verschure P.F.M.J. , Zimmerli L.
Published: April 2007

The process of developing a successful stroke rehabilitation methodology requires four key components: a good understanding of the pathophysiological mechanisms underlying this brain disease, clear neuroscientific hypotheses to guide therapy, adequate clinical assessments of its efficacy on multiple timescales, and a systematic approach to the application of modern technologies to assist in the everyday work of therapists. Achieving this goal requires collaboration between neuroscientists, technologists and clinicians to develop well-founded systems and clinical protocols that are able to provide quantitatively validated improvements in patient rehabilitation outcomes. In this article we present three new applications of complementary technologies developed in an interdisciplinary matrix for acute-phase upper limb stroke rehabilitation – functional electrical stimulation, arm robot-assisted therapy and virtual reality-based cognitive therapy. We also outline the neuroscientific basis of our approach, present our detailed clinical assessment protocol and provide preliminary results from patient testing of each of the three systems showing their viability for patient use.
Risk Factors for Mortality of Nosocomial Bacteraemia in Intensive Care Units
Authors: Çağatay A. Atahan , Özcan Perihan Ergin , Gulec Leyla , Ince Nurhan , Tugrul Simru , Özsüt Halit , Cakar Nahit , Esen Figen , Eraksoy Haluk , Calangu Semra
Published: April 2007

Objective: The aim of this study was to follow critically ill patients prospectively in intensive care units (ICUs) to determine risk factors for mortality and outcome associated with nosocomial bacteraemia (NB). Subjects and Methods: A case-control study of 176 patients was conducted to identify the risk factors for mortality of NB in ICU patients. The study was performed in emergency, surgical and general surgical ICUs with 23 beds during a 15-month period. A total of 1,450 patients were admitted to the ICUs during the study period. The USA Center for Disease Control and Prevention definitions were used to diagnose nosocomial infections. Nosocomial bacteraemia was defined as the isolation of one or more organisms from blood cultures taken at least 48 h after admission, which were not related to a problem present on admission. An assessment of whether the isolated organisms represented true bacteraemia rather than contamination was made by clinical or laboratory evidence of infection. Results: A total of 214 bacteraemia episodes were found in the 176 patients (64 female, 112 male; 51.3 ± 21.3 years old), 90 of whom died and 86 survived. The bacteraemia rate was 12.1%. The most common etiological agents of bacteraemia were Klebsiella pneumoniae: 46 (21.5%), methicillin-resistant Staphylococcus aureus: 46 (21.5%), Pseudomonas aeruginosa: 32 (14.9%), and Escherichia coli: 20 (9.3%). Multivariate analysis showed that the requirement of mechanical ventilation for more than 7 days (p < 0.001), total parenteral nutrition (p = 0.034), inotropic drug (p < 0.001), and increased creatinine level (p = 0.034) were independent risk factors for mortality of NB in ICUs. Conclusions: Nosocomial infections caused by Gram-negative bacteria continue to be one of the major sources of morbidity and mortality.
Cardiac Memory versus Likelihood of Ischemic Heart Disease in Hypertensive Patients with Ventricular Repolarization Abnormalities after Repetitive Uniform Ventricular Extrasystoles
Authors: Hegazy Aly Mohamad , Alkandary Mohamad Hussein
Published: April 2007

Objectives: To investigate the value of T-wave inversion after premature ventricular complexes (PVCs) for the prediction of hypertensive patients with a likelihood of ischemic heart disease (IHD). Patients and Methods: Ambulatory 24-hour ECG, ambulatory 24-hour blood pressure (BP) recording, echocardiography, treadmill exercise ECG test and thallium-201 scintigraphy were performed for 210 hypertensive patients. Results: Predictive indices showed that persistent symmetrical T-wave inversion after repetitive uniform PVCs equaling 30 min can be considered an indicator for the prediction of IHD in hypertensive patients as sensitivity was 80%, specificity: 73%, accuracy: 78%, positive predictive value: 83%, and negative predictive value: 69%. kappa coefficient value (ĸ) indicated that there was good agreement between changes in ventricular repolarization after PVCs and stress thallium scintigraphy (ĸ = 0.897). Receiver-operating characteristic curve data showed that the ideal cutoff value of T-wave inversion voltage to predict IHD in hypertensive patients was 2.2 mV (sensitivity: 66% and false positive: 35%, and area under curve: 0.716), but the ideal cutoff value of time for resolution of T-wave inversion was 34 min (sensitivity: 83% and false positive: 18%, and area under curve: 0.873). Multivariate analysis revealed that T-wave inversion after repetitive uniform PVCs was significantly associated with non-sustained ventricular tachycardia, decreased parasympathetic activity, increased sympathetic activity, morning BP surge, systolic BP load >50% and left ventricular diastolic dysfunction status. Conclusion: The data show that persistent symmetrical T-wave changes following resumption of sinus rhythm after repetitive uniform PVCs are an independent variable for the prediction of IHD in hypertensive patients.
Classifying Intertrochanteric Fractures of the Proximal Femur: Does Experience Matter?
Authors: Fung Wayne , Jönsson Anders , Bühren Volker , Bhandari Mohit
Published: April 2007

Objective: This prospective study aimed to evaluate inter-observer agreement of the AO/OTA and Evans/Jensen classification systems with an emphasis on the effect of reviewer experience. In addition, the level of agreement in the determination of fracture stability across varying levels of experience was evaluated. Subject and Methods: A group of 12 reviewers (6 surgeons, 3 senior residents, 3 junior residents) independently assessed 56 radiographs of intertrochanteric hip fractures and classified them using the AO/OTA and Evans/Jensen systems. Reviewers further assessed the stability of the fracture patterns. Results: Overall, higher agreement was obtained for the AO/OTA classification than with the Evans/Jensen classification. However, neither classification system met acceptable thresholds for reliability. Surgeons were unable to reliability determine if fractures were stable or unstable. Increased experience improved AO/OTA classification reliability and assessment of stability but decreased agreement in the Evans/Jensen classification. Conclusion: The AO/OTA classification should be used in favor of the Evans/Jensen classification whenever possible. Our findings suggest that surgeons’ perceptions about stability vary to a significant extent thereby necessitating clear definitions of stability.
Development, Validation and Application of Tandem Mass Spectrometry for Screening of Inborn Metabolic Disorders in Kuwaiti Infants
Authors: Abdel-Hamid Mohammed , Tisocki Klara , Sharaf Laila , Ramadan Dina
Published: April 2007

Objective: The aim of this work was to develop a specific and validated tandem mass spectrometric (MS/MS) method for screening of amino acidopathies, organic acidurias, urea cycle disorders and fatty acid oxidation defects in Kuwaiti newborns and sick infants. Materials and Methods: A total of 1,520 blood samples were tested for inborn metabolic disorders in Kuwaiti newborns and sick infants. Positive electrospray MS/MS was used to measure diagnostic acylcarnitines and amino acids in blood spots after simple extraction and derivatization procedures. Validation and stability studies were conducted using control blood samples supplemented with known concentrations of the diagnostic amino acids or acylcarnitines. Reference and cutoff levels of the diagnostic metabolites were determined in a group of 500 normal Kuwaiti babies for quantitative evaluation. Results: Of the 1,520 samples, 32 were positive newborn cases and 27 positive symptomatic infants. For the validation studies, the range of relative standard deviation was 2.6–14.7%, whereas the range of the percent deviation from nominal concentrations was –23.0 to +25.0 of the diagnostic metabolites. Stability studies indicated appropriate stability of the diagnostic amino acids and acylcarnitines in dried blood spots stored at 22 ± 1°C and relative humidity of 50–60%. Conclusions: Tandem mass spectrometry can significantly contribute to a newborn screening program as a fast and highly specific diagnostic technique for screening of a broad range of inborn metabolic disorders.
Correlation between Increased Serum sFas Levels and Microalbuminuria in Type 1 Diabetic Patients
Authors: Protopsaltis John , Kokkoris Stelios , Nikolopoulos George , Spyropoulou Panagiota , Katsaros Thomas , Salvanos Leonardos , Brestas Paris , Korantzopoulos Panagiotis , Melidonis Andreas
Published: April 2007

Objective: The aim of this study was to elucidate if apoptosis dysregulation is present in type 1 diabetic patients with microalbuminuria. Subjects and Methods: The following variables were determined in 29 type 1 diabetic patients: the duration of diabetes, soluble Fas (sFas), Bcl-2, hemoglobin A1c levels, glomerular filtration rate (GFR) and microalbuminuria, using the urine albumin to urine creatinine ratio (ACR). Age and gender were assessed and patients were categorized into two groups, according to their ACR: the microalbuminuric (MA) group with an ACR ≧30 mg/g, and the normoalbuminuric (NA) group with an ACR <30 mg/g. Results: The differences between the two groups regarding sFas, Bcl-2 and GFR were not statistically significant. However, in the MA group, a significant positive relationship between sFas and ACR was observed (r = 0.736, p = 0.015). Dividing patients into two subgroups – mild versus severe (ACR ≧150 mg/g) microalbuminuric patients – significant differences in sFas (60.4 vs. 87.2 pg/ml; p = 0.047) and GFR (113 vs. 69.5 ml min–1 1.73 m–2; p = 0.021) were observed, whereas in Bcl-2, the difference was not significant (77.96 vs. 71.13 ng/ml). Conclusions: At the early stages of diabetic nephropathy in type 1 diabetic patients, there seems to be a dysregulation of apoptosis, as expressed by enhanced sFas levels, leading to the speculation that the prevalence of antiapoptotic mechanisms (sFas) may promote mesangial proliferation.
Role of Urinary Cytology in Detecting Human Polyoma BK Virus in Kidney Transplant Recipients
Authors: Kapila Kusum , Nampoory Mangalathillom R.N. , Johny Kaivilayil V. , Pacsa Alexander S. , Al-Ayadhy Bushra , Mathew Jessy R. , Nair Madhavan P. , Halim Medhat A. , George Sara S. , Francis Issam M.
Published: April 2007

Objective: To report data on the evaluation of the efficacy of urine cytology in detecting BK virus (BKV). Material and Methods: Papanicolaou-stained cytospin preparations of randomly collected urine samples from 8 renal transplant (RTR) patients (5 males, 3 females, age: 23–63 years) who previously tested positive for BKV by PCR in urine or blood or both were studied. Urine sediment from 3 of the patients was processed for ultrastructural examination (EM). Renal biopsies before and after BKV detection were also evaluated. Results: The interval between renal transplant and urine cytology ranged between 2 and 5 years. Urine from females was difficult to assess due to vaginal contamination. In 2 of the 5 urine specimens from male recipients BKV-infected decoy cells were identified. Viral particles suggestive of BKV were identified on EM in 2 of the 3 specimens studied. Kidney biopsies showed morphologic features suggestive of BKV infection in 2 cases, 1 each detected on cytology and EM, respectively. Conclusion: Screening for the presence of decoy cells in urine provides a simple sensitive means for the diagnosis of BKV nephropathy in RTR.
Prevalence of Malaria during Pregnancy and Antimalarial Intervention in an Urban Secondary Health Care Facility in Southern Nigeria
Authors: Enato Ehijie F.O. , Okhamafe Augustine O. , Okpere Eugene E. , Oseji Frederick I.
Published: April 2007

Objective: To investigate the prevalence of malaria during pregnancy and antimalarial interventions in an urban secondary health care facility. Subjects and Methods: Of 432 pregnant women who delivered or were attending an antenatal clinic in a secondary health care facility in Benin City, Nigeria, 199 were recruited for the study. Demographic data were obtained from the pregnant women at delivery, and maternal peripheral, placental, and cord blood samples were collected for microscopy. Among the antenatal clinic attendees, a questionnaire was used to assess their antimalarial preventive measures. Results: Of the 199 pregnant women, 60 (30%) reported that they had had malaria during the preceding 3 months, and a majority of them (85%) used chloroquine. Almost all reported the drug was efficacious (98%) and well tolerated (80%). Only 18 (13%), 14 (10%), and 2 (1%) of the women had positive maternal peripheral, placental, and cord blood parasitaemia, respectively. The geometric mean (± SD) numbers of malaria parasites per microliter were 636.06 ± 1,450.11 in peripheral blood, 4,250.36 ± 13,866.01 in placental blood, and 59.50 ± 27.58 in umbilical cord blood. Only 31 (12%) and 13 (5%) of antenatal women believed in the efficacy of insecticide-treated bed nets or sulphadoxine/pyrimethamine-based intermittent preventive therapy as antimalarial preventive measures, respectively, while 23 (9%) and 31 (12%), respectively, reported they currently use them. Conclusions: Despite the common occurrence of malaria during pregnancy, there was a limited knowledge and use of the recommended antimalarial interventions by pregnant women attending the antenatal clinic of this health care facility. There is, therefore, an urgent need to increase the implementation of antimalarial interventions during pregnancy.