bluuebunny/crossref_metadata_2025 huggingface dataset:
E‐cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: A comparison of E‐cadherin with desmosomal components
Authors: Bosch Franz X. , Andl Claudia , Abel Ulrich , Kartenbeck Jürgen
Published: December 2004

E‐cadherin‐mediated and desmosomal cell‐cell adhesion have been implicated in the suppression of invasive and metastatic behavior of squamous cell carcinomas. Whether the adhaerens junction represented by E‐cadherin and the desmosomes interplay or have distinct and separate roles in squamous cell cancer progression is still unclear. We have studied a cohort of 200 primary tumors and 56 lymph node metastases from different anatomic sites of the head and neck region for changes in synthesis of E‐cadherin, desmoplakin and desmoglein by immunohistochemistry (IHC). Selected cases were studied by indirect immunofluorescence (IIF) and electron microscopy (EM). Only frozen sections were evaluated since they gave stronger and reproducible staining results. IHC data obtained were compared to clinical parameters. While some reduction in immunostaining was found in virtually all invasive tumors, at least partial expression, including that of E‐cadherin, persisted in most late stage tumors and in lymph node metastases. Reduced desmosomal staining correlated with desmosomes reduced in numbers, size or in structural defects by EM analysis. By univariate analysis, reduction in synthesis of both E‐cadherin and the desmosomal components that were generally linked (i.e., they showed positive rank correlations) were significantly associated with clinical parameters including overall and disease‐free survival. However, by multivariate analysis including a Cox proportional hazards regression model (backward selection), the desmosomal components were not significant as independent prognostic factors. By contrast, E‐cadherin was strongly associated with patient prognosis. In line with the highly significant association of reduced E‐cadherin synthesis with an increased relative risk of follow up events, i.e., regional lymph node (p = 0.0007) and distant metastasis (p < 0.0001), as well as local recurrences (p < 0.0001), the prognostic strength of E‐cadherin was independent of and stronger than histological grading, N stage, tumor site, and even stronger than the TNM stage. Based on these results, evaluation of E‐cadherin in squamous cell carcinomas by immunostaining is recommended as a significant prognostic marker. © 2004 Wiley‐Liss, Inc.
Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk
Authors: Sakiyama Tokuki , Kohno Takashi , Mimaki Sachiyo , Ohta Tsutomu , Yanagitani Noriko , Sobue Tomotaka , Kunitoh Hideo , Saito Ryusei , Shimizu Kimiko , Hirama Chie , Kimura Junko , Maeno Go , Hirose Hiroshi , Eguchi Takashi , Saito Daizo , Ohki Misao , Yokota Jun
Published: December 2004

Single nucleotide polymorphisms (SNPs) were searched for in 36 genes involved in diverse DNA repair pathways, and 50 nonsynonymous (associated with amino acid changes) SNPs identified were assessed for associations with lung cancer risk by a case‐control study consisting of 752 adenocarcinoma cases, 250 squamous cell carcinoma cases and 685 controls. An SNP, Arg72Pro, of the TP53 gene encoding a DNA damage response protein showed the strongest association with squamous cell carcinoma risk (OR Pro/Pro vs. Arg/Arg = 2.2), while 2 other SNPs, Phe257Ser of the REV gene encoding a translesion DNA polymerase and Ile658Val of the LIG4 gene encoding a DNA double‐strand break repair protein, also showed associations (OR Ser/Ser vs. Phe/Phe = 2.0 and OR Ile/Val vs. Ile/Ile = 0.4, respectively). An SNP, Thr706Ala, in the POLI gene encoding another translesion DNA polymerase was associated with adenocarcinoma and squamous cell carcinoma risk, particularly in individuals of ages < 61 years (OR Ala/Ala + Ala/Thr vs. Thr/Thr = 1.5 and 2.4, respectively). POLI is the human counterpart of PolI, a strong candidate for the Par2 (pulmonary adenoma resistance 2) gene responsible for adenoma/adenocarcinoma susceptibility in mice. The present results suggest that these 4 SNPs function as genetic factors underlying lung cancer susceptibility by modulating activities to maintain the genome integrity of each individual. © 2004 Wiley‐Liss, Inc.
Bowes melanoma cells secrete heregulin, which can promote aggregation and counteract invasion of human mammary cancer cells
Authors: Stove Christophe , Boterberg Tom , Van Marck Veerle , Mareel Marc , Bracke Marc
Published: December 2004

Invasiveness, the ability of cancer cells to migrate beyond the normal tissue boundaries, often leads to metastasis and thereby usually turns cancer into a fatal disease. At the molecular level, the E‐cadherin/catenin complex is an example of a powerful invasion suppressor in epithelial cells. Since the absence of melanocytes has been associated with disturbances in epithelial organization, we decided to investigate the influence of molecules secreted by melanocytes on the function of the E‐cadherin/catenin complex. We used the Bowes melanoma cell line as a source of such molecules. The conditioned medium of Bowes melanoma stimulated aggregation of human MCF‐7/6 mammary adenocarcinoma cells at short (30 min) and long (24–72 hr) notice. This effect could be inhibited by MB2, an antibody against human E‐cadherin. Conditioned medium of Bowes melanoma also inhibited invasion of MCF‐7/6 cells into precultured chick heart fragments. Candidate molecules such as insulin, insulin‐like growth factor I, follistatin and interleukins were ruled out to be responsible for the effects, but heregulin mimicked some of the effects of the conditioned medium. Our data indicate that heregulin stimulates aggregation and inhibits invasion of MCF‐7/6 cells via activation of the E‐cadherin/catenin complex. © 2005 Wiley‐Liss, Inc.
Naturally processed and HLA‐B8‐presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer
Authors: Oerke Sebastian , Höhn Hanni , Zehbe Ingeborg , Pilch Henryk , Schicketanz Karl‐Heinz , Hitzler Walter E. , Neukirch Claudia , Freitag Kirsten , Maeurer Markus J.
Published: December 2004

Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein to T cells. We describe an overrepresentation of the HLA‐B8 allele (28.44%) in cervical cancer patients as compared to the MHC class I allele frequency in a local healthy control population (18.80%) and the identification of an HLA‐B8‐binding peptide TLHEYMLDL (HPV16 E77–15), which is able to drive HPV16 E7‐specific and MHC class I‐restricted T‐cell responses in peripheral blood lymphocytes from healthy individuals. TLHEYMLDL‐specific T cells recognize the naturally processed and presented peptide on HPV16+ cervical cancer cells transfected with the HLA‐B8 gene defined by IFN‐γ production. This peptide epitope is also recognized by freshly harvested tumor‐infiltrating T cells or T cells from tumor‐draining lymph nodes from patients with cervical cancer determined by flow cytometry as well as by tetramer in situ staining. HLA‐B8‐restricted HPV E77–15‐specific T cells reside predominantly in the CD8+ CD45RA+ CCR7+ precursor or in the differentiated CD8+ CD45RA+ CCR7− T‐cell population. © 2004 Wiley‐Liss, Inc.
p‐Adic Colombeau‐Egorov type theory of generalized functions
Authors: Albeverio S. , Khrennikov A. Yu. , Shelkovich V. M.
Published: December 2004

The p‐adic Colombeau‐Egorov algebra of generalized functions on ℚnp is constructed. For generalized functions the operations of multiplication, Fourier‐transform, convolution, taking pointvalues are defined. The operations of (fractional) partial differentiation and (fractional) partial integration are introduced by the Vladimirov's pseudodifferential operator. The products of Bruhat‐Schwartz distributions are well defined as elements of this algebra. In contrast to the “usual” Colombeau and Egorov ℂ‐theories, where generalized functions on ℝn are not determined by their pointvalues on ℝn, p‐adic Colombeau‐Egorov generalized functions are uniquely determined by their pointvalues on ℚnp. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Low degree 3‐folds in P6
Authors: Bertolini Marina , Fania Maria Lucia
Published: December 2004

In this paper we construct new smooth varieties of dimension 3 in P6, with degree 12 ≤ d ≤ 15 and we also give different constructions for some known varieties. Moreover we determine the adjunction theoretic structure of all the varieties that we deal with. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Generalization of a class of nonlinear averaging integral operators
Authors: Bulboacă Teodor
Published: December 2004

Let H(U) be the space of all analytic functions in the unit disk U, and let coE denote the convex hull of the set E ⊂ ℂ. If K ⊂ H(U) then the operator I : K → H(U) is said to be an averaging operator if

For a function h ∈ A ⊂ H(U) we will determine simple sufficient conditions on h such that

for all f ∈ ℳ︁′1/β, where

and ℳ︁′1/β represents the class of 1/β‐convex functions (not necessarily normalized).

As an application, we will give sufficient conditions on h to insure that the operators Ih;β,γ are averaging operators on certain subsets of H(U), in order to generalize the result of [5]. In addition, some particular cases of this result obtained for appropriate choices of the function h will also be given. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Witten triples and the Seiberg–Witten equations on a complex surface
Authors: Dürr Markus
Published: December 2004

We study the solutions of the Seiberg–Witten equations on complex surfaces. We show that for a large class of parameters, the gauge equivalence classes of irreducible solutions of the twisted Seiberg–Witten equations correspond to stable Witten triples. We prove that on Kähler surfaces this correspondence is the set‐theoretical support of an isomorphism of real‐analytic spaces. This makes it possible to take multiplicities into account and generalizes and unifies results previously obtained by Witten. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Limiting reiteration for real interpolation with slowly varying functions
Authors: Gogatishvili Amiran , Opic Bohumír , Trebels Walter
Published: December 2004

We present reiteration formulae with limiting values θ = 0 and θ = 1 for a real interpolation method involving slowly varying functions. Applications to the Lorentz–Karamata spaces, the Fourier transform and the Riesz potential are given. In particular, our results yield improvements of limiting Sobolev‐type embeddings due to Trudinger, Hansson, Brézis and Wainger, Edmunds, Gurka and Opic, Fusco, Lions and Sbordone, et al., and they are related to those of Edmunds, Kerman and Pick, or Pustylnik. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effective finiteness theorems for maps between canonically polarizedcompact complex manifolds
Authors: Heier Gordon
Published: December 2004

Effective bounds for the finite number of surjective holomorphic maps between canonically polarized compact complex manifolds of any dimension with fixed domain are proven. Both the case of a fixed target and the case of varying targets are treated. In the case of varying targets, bounds on the complexity of Chow varieties are used. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Oscillation criteria for nonlinear differential equations with integrable coefficient
Authors: Hong Huei‐Lin , Yeh Cheh‐Chih , Hong Chen‐Huang
Published: December 2004

In this paper, we consider the oscillation of the nonlinear differential equation

We obtain a new sufficient condition for any nonoscillatory solution y(t) of the above equation satisfying lim inft→∞ |y(t)| = 0. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Comparative analysis of HIV‐1 Tat variants
Authors: Pantano Sergio , Carloni Paolo
Published: December 2004

HIV‐1 Tat protein is a crucial element for viral replication; therefore, its inhibition might be exploited against the AIDS infection. To gain insights on the natural variability of this protein, we present a comparative investigation on the relationship between the primary sequences and the experimentally available three‐dimensional structures from the HIV‐1 Tat variants Z2, BRU, and MAL. Our computational tools include sequence conservation algorithms, structural analysis, electrostatic modeling, and molecular dynamics (MD) simulations. We find that two regions located between residues 10–18 and 41–52 display the highest primary sequence conservation, while the most conserved region among the available structures corresponds approximately to the segment between positions ∼44 and 50. Furthermore, in spite of their large structural divergence, Tat variants share a common mode for long‐range intramolecular interactions. Finally, the flexibility of the Z2, BRU, and MAL variants, as emerging from multinanosecond MD simulations, is rather similar. Based on this work, we conclude that the turnlike region between amino acids 44 and 50 is structurally most conserved, emerging as an important motif for pharmaceutical targeting aimed toward inhibiting Tat action. Proteins 2005. © 2004 Wiley‐Liss, Inc.
FAST: A novel protein structure alignment algorithm
Authors: Zhu Jianhua , Weng Zhiping
Published: December 2004

We present a novel algorithm named FAST for aligning protein three‐dimensional structures. FAST uses a directionality‐based scoring scheme to compare the intra‐molecular residue–residue relationships in two structures. It employs an elimination heuristic to promote sparseness in the residue‐pair graph and facilitate the detection of the global optimum. In order to test the overall accuracy of FAST, we determined its sensitivity and specificity with the SCOP classification (version 1.61) as the gold standard. FAST achieved higher sensitivities than several existing methods (DaliLite, CE, and K2) at all specificity levels. We also tested FAST against 1033 manually curated alignments in the HOMSTRAD database. The overall agreement was 96%. Close inspection of examples from broad structural classes indicated the high quality of FAST alignments. Moreover, FAST is an order of magnitude faster than other algorithms that attempt to establish residue–residue correspondence. Typical pairwise alignments take FAST less than a second with a Pentium III 1.2GHz CPU. FAST software and a web server are available at http://biowulf.bu.edu/FAST/. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Protein conformational transitions coupled to binding in molecular recognition of unstructured proteins: Deciphering the effect of intermolecular interactions on computational structure prediction of the p27Kip1 protein bound to the cyclin A–cyclin‐dependent kinase 2 complex
Authors: Verkhivker Gennady M.
Published: December 2004

The relationship between folding mechanism coupled to binding and structure prediction of the tertiary complexes is studied for the p27Kip1 protein which has an intrinsically disordered unbound form and undergoes a functional folding transition during complex formation with the phosphorylated cyclin A–cyclin‐dependent kinase 2 (Cdk2) binary complex. Hierarchy of p27Kip1 structural loss determined in our earlier studies from temperature–induced Monte Carlo simulations and subsequent characterization of the transition state ensemble (TSE) for the folding reaction have shown that simultaneous ordering of the p27Kip1 native intermolecular interface for the β‐hairpin and β‐strand secondary structure elements is critical for nucleating a rapid kinetic transition to the native tertiary complex. In the present study, we investigate the effect of forming specific intermolecular interactions on structure prediction of the p27Kip1 tertiary complex. By constraining different secondary structure elements of p27Kip1 in their native bound conformations and conducting multiple simulated annealing simulations, we analyze differences in the success rate of predicting the native structure of p27Kip1 in the tertiary complex. In accordance with the nucleation–condensation mechanism, we have found that further stabilization of the native intermolecular interface for the β‐hairpin and β‐strand elements of p27Kip1, that become ordered in the TSE, but are hardly populated in the unbound state, results in a consistent acquisition of the native bound structure. Conversely, the excessive stablization of the local secondary structure elements, which are rarely detected in the TSE, has a detrimental effect on convergence to the native bound structure. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Implicit solvent simulations of peptide interactions with anionic lipid membranes
Authors: Lazaridis Themis
Published: December 2004

A recently developed implicit membrane model (IMM1) is supplemented with a Gouy–Chapman term describing counterion‐screened electrostatic interactions of a solute with negatively charged membrane lipids. The new model is tested on peptides that bind to anionic membranes. Pentalysine binds just outside the plane of negative charge, whereas Lys‐Phe peptides insert their aromatic rings into the hydrophobic core. Melittin and magainin 2 bind more strongly to anionic than to neutral membranes and in both cases insert their hydrophobic residues into the hydrocarbon core. The third domain of Antennapedia homeodomain (penetratin) binds as an α‐helix in the headgroup region. Cardiotoxin II binds strongly to anionic membranes but marginally to neutral ones. In all cases, the location and configuration of the peptides are consistent with experimental data, and the effective energy changes upon binding compare favorably with experimental binding free energies. The model opens the way to exploring the effect of membrane charge on the location, conformation, and dynamics of a large variety of biologically active peptides on membranes. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Reflections on the road not (yet) taken: How a centralized public strategy can help youth work focus on youth
Authors: Pittman Karen J.
Published: December 2004

Karen Pittman calls for innovation and systemic change in the U.S. youth work by examining the key values of the United Kingdom's national youth work system.
Professional development in the youth development field: Issues, trends, opportunities, and challenges
Authors: Quinn Jane
Published: December 2004

This chapter reviews key issues in professional development in the youth development field, describing important work done over the past two decades and lessons learned from major philanthropic investments in capacity building both nationally and locally.
A Novel Polyoxovanadium Cluster Shell: β‐As8V14O42
Authors: Zheng Shou‐Tian , Zhang Jie , Yang Guo‐Yu
Published: December 2004

The hydrothermal reaction of VOSO4, As2O5, piperazine and H2O produces [H2N(CH2)4NH2]4[β‐As8V14O42(SO4)]·2HSO4 (1), which is the first arsenic‐vanadium cluster containing a spherical β‐As8V14O42 shell. The structure of this compound was characterized by single crystal X‐ray diffraction, elemental analysis, TG, and IR spectrum. Crystal data for 1: Orthorhombic, Cmcm, a = 15.369(1) Å, b = 16.404(1) Å, c = 25.772(1) Å, V = 6497.4(9) Å3, Z = 4.
Synthesen und Kristallstrukturen neuer sulfidoverbrückter Rutheniumclusterverbindungen
Authors: Wunder Markus , Eckermann Amanda L. , Rauchfuss Thomas B. , Fenske Dieter
Published: December 2004

Durch die Reaktion von S(SiMe3)2 bzw. NaSH mit [RuCl2(PPh3)3], bzw. [Ru3Cl8(PEt3)4] können sulfidoverbrückte Rutheniumclusterverbindungen dargestellt werden. Im folgenden werden die Verbindungen [Ru6S8(PPh3)6][PF6] (1), [Ru6S8(PPh3)6][RuCl4(PPh3)2] (2), [Ru6S8(PEt3)6] (3) und [Ru3S4Cl2(PPh3)3]2 (4) beschrieben. Die Strukturen dieser Verbindungen wurden mittels Einkristall‐Röntgenstrukturanalyse aufgeklärt.
Editorial
Authors: COX GORDON , PITTS STEPHANIE
Published: December 2004

All research starts with identifying a problem, drawing on a firm knowledge of a particular context aswell as the literature relating to the problem and its potential solutions. For music educators these problems are usually located in some aspect of their practice as teachers. It is this connection between research and practice that has been at the heart of this journal since its inception.
Opioid therapy of chronic pain: Assessment of consequences
Authors: Savage S. R.
Published: December 2004

This paper will review what is known about key issues of importance in the clinical use of opioids for the treatment of intractable non‐cancer related pain, and will attempt to describe the evolving areas of consensus among clinicians who treat pain and addiction regarding various aspects of use of opioids for the treatment of chronic non‐cancer pain.
Opioid use in cancer pain. Is a more liberal approach enhancing toxicity?
Authors: Daeninck P. J. , Bruera E.
Published: December 2004

The majority of cancer patients develop pain before death. This pain has been shown to be underdiagnosed and undertreated. Opioid use has increased in the past 20 years in both developing and developed countries. The changing pattern in opioid use has resulted in the emergence of neurotoxicity as a major side effect of the treatment of cancer pain. The syndrome of opioid‐induced neurotoxicity (OIN) encompasses delirium, hallucinosis, myoclonus/seizures and hyperalgesia. Increased vigilance can lead to the timely diagnosis of OIN, and strategies for its treatment can be implemented with encouraging results. Identification and modification of risk factors for the development of OIN can help in its prevention and improve the quality of life in advanced cancer patients.
Methodological issues in the assessment of health‐related quality of life in palliative care trials
Authors: Groenvold M.
Published: December 2004

Palliative care aims at improving the patient’s quality of life. Clinical trials, therefore, often include the patient’s subjective evaluation of symptoms and psychosocial problems, so‐called health‐related quality of life (HRQL), as end‐points. Unfortunately, there are frequently methodological weaknesses in the assessment of HRQL. This paper discusses four criteria which can be used in the evaluation of the quality of such studies: I. The authors should document that they have included the relevant HRQL issues in the questionnaire. If a trial misses important issues, its results may be misleading. II. The sample size should be sufficient to detect meaningful differences. Many trials are too small. III. The assessment of HRQL should have the appropriate timing, reflecting the research questions. The symptoms and the benefit resulting from treatments are not constant over time and often have cyclic patterns. The results may therefore be dependent on the timing of the administration of questionnaires to patients and on the time frames specified in the instructions. IV. The data must be reasonably complete. Incomplete data cannot be avoided in palliative care research, but missing data due to administrative failures or unrealistic schedules must be avoided. A pilot study may show whether a study is feasible. Missing data are likely to bias results. Many published palliative care studies are suboptimal with regard to one or more of these four criteria. This should be considered when reading published studies and when new trials are planned.
Economic implications of pain management
Authors: Loeser J. D.
Published: December 2004

Background: Economic issues in pain management affect the patient, the provider and society. This paper will review some of the data on the costs to society of chronic pain and its associated disability. It will also look at the costs to patient and provider of alternative economic models. Conceptual issues that underlie health care delivery and the attendant costs must be addressed if society is to gain control over runaway health care costs and reduce the economic burden of chronic pain and disability for the patient as well as the provider.

Methods: Literature review and synthesis.

Results: Chronic pain is the primary cause of health care consumption and disability in the working years. Multidisciplinary pain clinics have proven utility. Data on efficacy of most other kinds of care is lacking. Disability costs are related to conceptual inadequacies and the medicalization of post‐industrial societies.

Conclusion: To control inappropriate care and escalating costs, we must change concepts of pain and disability and the methods of funding both of these in relation to chronic pain. The outcome of the continuing struggle between the profession of medicine, the state and capitalists will determine how and whether pain management is a part of medical care.
Elevation of interleukin‐6 levels in cervical secretions as a predictor of preterm delivery
Authors: Lange Melanie , Chen Frank K. , Wessel Jens , Buscher Ulrich , Dudenhausen Joachim W.
Published: December 2004

Background. The objective of this study was to evaluate the predictive value of interleukin‐6 (IL‐6) in cervical secretions for preterm delivery before 34+0 gestational weeks in patients with preterm labor.

Methods. In this prospective study, 31 patients were enrolled with preterm labor and intact membranes. Cervical swabs were taken on admission and the concentration of IL‐6 was measured. The gestational age at the time of admission and delivery, as well as the time interval to delivery, were evaluated and compared with the concentration of IL‐6 on admission.

Results. Cervical IL‐6 was significantly elevated in the preterm delivery group (< 34+0 gestational weeks, p < 0.05). Choosing 20 pg/ml as a cut‐off concentration, cervical IL‐6 had a sensitivity and negative predictive value of 100%, a specificity of 67% and a positive predictive value of 47%. Concerning the time interval to delivery, the sensitivity of IL‐6 was 100% and the specificity 57% for delivery within 2 days and 100% and 64% for delivery within 7 days.

Conclusions. Cervical IL‐6 is a new, promising diagnostic tool to identify patients at high risk of preterm delivery.
Preterm delivery: an overview
Authors: Haram Kjell , Mortensen Jan Helge Seglem , Wollen Anne‐Lone
Published: December 2004

Preterm delivery is the leading factor causing neonatal mortality and morbidity. We have conducted a PubMed literature search to obtain an update on the etiology, diagnostic problems and therapeutic considerations of preterm delivery. Approximately 5–10% of all births are premature. Preterm labor is associated with preterm rupture of membranes, cervical incompetence, polyhydramnion, fetal and uterine anomalies, infections, social factors, stress, smoking, heavy work and other risk factors. The diagnosis is made on the patients presenting symptoms, clinical findings and of progressive effacement and dilatation of the cervix. Biochemical markers of preterm delivery are of minor importance in daily clinical work. Measurement of the cervix, however, is a practical and valuable tool to predict preterm delivery. Cervical cerclage can be useful in selected cases. Antibiotics may help to prevent preterm labor in cases of known etiologic agents (e.g. preterm rupture of membranes and urinary infection). The use of tocolytic agents such as β‐sympathetic receptor stimulators can be advocated for a few days. There is evidence that their long‐term use is not beneficial and could even be harmful to the fetus. Calcium channel blockers (nifedipine) and a new selective oxytocin receptor antagonist, atosiban, appear to be as effective as β‐sympathomimetic drugs on uterine contractions with fewer side‐effects. Prostaglandin synthetase inhibitors such as indomethacin may prevent uterine contractions and can be used prior to the 32nd week of pregnancy. A single course of corticosteroid treatment in two doses of 12 mg betamethasone or 6 mg of dexamethasone is important for the prevention of respiratory distress between the 24th and 34th weeks of pregnancy. Multiple doses may be harmful and should be avoided. In these cases management should depend on gestation age (fetal maturity). Uterine contractions after 34 weeks' gestation are not an indication for tocolytic treatment.
Amniotic membrane transplantation elicits goblet cell repopulation after conjunctival reconstruction in a case of severe ocular cicatricial pemphigoid
Authors: Barabino Stefano , Rolando Maurizio
Published: December 2004

Purpose:  The surgical procedures used until now to rebuild the conjunctiva in patients affected by ocular cicatricial pemphigoid (OCP) have not demonstrated appreciable anatomical and functional success. This study reports the postoperative clinical and cytological outcomes of a human amniotic membrane transplantation (AMT) to rebuild the conjunctiva in a case of late stage OCP.

Methods:  We present a 75‐year‐old woman with a severe form of pemphigoid with entropion, trichiasis, symblepharon and blunting of the fornices, who underwent excision of the scarred and inflamed tissue covering the ocular surface and AMT.

Results:  Our data show an improvement of the ocular surface condition, with reacquired fornix depth, reduced inflammation and presence of goblet cells at each follow‐up.

Conclusion:  Amniotic membrane transplantation was successful as a first step procedure to reduce inflammation and to rebuild a physiological conjunctival epithelium in late stage OCP.
Three unpublished collections of South Arabian coins
Authors: Davidde Barbara
Published: December 2004

The author presents the South Arabian holdings of three museums in Israel, forty‐eight coins in all. The coins comprise one Qatabanian coin and several coins each of three very common Himyarite and Sabaean types (two issues of ‘Amdân Bayyin Yuhaqbid, kingdom of Saba’ and dhû Raydân, and various coins of the Sabaean Bucranium series). The paper gives the opportunity to make some remarks on South Arabian Coinage.
D3 dopamine receptor mRNA expression in lymphocytes: a peripheral marker for schizophrenia?
Authors: van der Weide J. , W. Steijns L. S. , van der Geld M. A. M. , de Groot P. A.
Published: December 2004

Background:

Identification of schizophrenia, a common neuropsychiatric disorder, is based on clinical examination. An easily measurable peripheral marker, which may enable a more rapid and more accurate diagnosis, is not available. A possible candidate is the D3 dopamine receptor on lymphocytes.

Objective:

The D3 receptor is investigated for its clinical significance as a marker for diagnosing schizophrenia.

Methods:

From eight schizophrenic patients and eight controls lymphocyte RNA was isolated. A semiquantitative reverse transcription–polymerase chain reaction (RT-PCR) was carried out and the intensities of the specific D3 dopamine receptor bands of patients and controls were compared.

Results:

No difference could be seen between the intensities of the bands from patients and controls.

Conclusion:

An aberrant D3 dopamine receptor mRNA expression in lymphocytes of schizophrenics could not be demonstrated. This might be caused by down-regulation of D3 receptor production by antipsychotic drug treatment. At present, the D3 receptor seems to have no diagnostic value in schizophrenia.
Hypothalamic digoxin and brain function
Authors: Kurup R. K. , Kurup P. A.
Published: December 2004

Background and objectives:

The study assessed the biochemical differences between right hemispheric-dominant and left hemispheric-dominant individuals. The chemical hemispheric-dominance in various systemic and neuropsychiatric diseases was also studied.

Methods:

The isoprenoid metabolites, digoxin, dolichol and ubiquinone, glycoconjugate metabolism, free radical metabolism and the RBC membrane composition, were studied in individuals with differing hemispheric-dominance. The digoxin levels and RBC membrane Na+-K+ATPase activity were also studied in systemic and neuropsychiatric diseases.

Results:

The results showed that right hemispheric-dominant individuals had elevated digoxin levels, increased free radical production and reduced scavenging, increased tryptophan catabolites and reduced tyrosine catabolites, increased glycoconjugate levels and increased cholesterol : phospholipid ratio of RBC membranes. Left hemispheric-dominant individuals had the opposite patterns. This patterns could be correlated with various systemic and neuropsychiatric diseases.

Conclusion:

Right hemispheric-dominance represents a hyperdigoxinaemic state with membrane sodium–potassium ATPase inhibition. Left hemispheric-dominance represents the reverse pattern with hypodigoxinaemia and membrane sodium–potassium ATPase stimulation. Hemispheric-dominance could predispose to various systemic and neuropsychiatric diseases.
Accidental out‐of‐hospital deliveries: an obstetric and neonatal case control study
Authors: Rodie Vanessa A. , Thomson Andrew J. , Norman Jane E.
Published: December 2004

Background. Accidental out‐of‐hospital (OHD) deliveries are associated with high rates of perinatal morbidity and mortality. The ability of health care workers to identify women at risk of out‐of‐hospital delivery is limited. The purpose of this study was to determine the prevalence of these deliveries in our population and to quantify the neonatal morbidity and mortality associated with such births. Further we aimed to determine whether women at risk of accidental out‐of‐hospital delivery in our population could be identified antenatally.

Methods. A retrospective case‐control study was performed. Women who delivered accidentally out‐of‐hospital in our catchment area between January 1995 and March 1999 were identified (cases) and compared with women who delivered in hospital following spontaneous labor (controls). Outcome measures included maternal demographic characteristics, obstetric features and neonatal outcome.

Results. In the study period, 117 women delivering 121 babies were identified who delivered accidentally out‐of‐hospital, (0.6% of all deliveries registered at the hospital). Women who delivered before arrival at hospital were more likely to be of greater parity, unbooked, late bookers and/or poor attenders for antenatal care. Gestation at delivery, duration of labor and birthweight were less in the out‐of‐hospital delivery group compared with the control group. The rate of perineal suturing was lower for cases than controls. Babies who were delivered accidentally out‐of‐hospital were more likely to require admission to the neonatal unit and had a higher perinatal mortality rate than controls (51.7 versus 8.6/1000 deliveries, respectively).

Conclusions. Accidental out‐of‐hospital deliveries account for less than 1% of deliveries in our population, but are associated with significant perinatal morbidity and mortality. Women should be educated regarding the importance of both antenatal care and a planned delivery. Since the majority of women who deliver accidentally out‐of hospital are parous, there is an opportunity to do this in a previous confinement.
Different hepatic vascular response to noradrenaline and histamine between guinea‐pig and rat
Authors: Shibamoto T. , Narushima M. , Ling Y.‐Q. , Shimo T. , Tsuchida H. , Kurata Y. , Ogura T.
Published: December 2004

Aim:  Hepatic xenotransplantation from guinea‐pig to rat has not been established. This failure is partly ascribed to differences in hepatic vascular characteristics between two species. However, the differences in hepatic vascular resistance distribution and responses to vasoconstrictors are not known. The present study was designed to determine basal levels of segmental vascular resistances and the responses to histamine and noradrenaline in isolated guinea‐pig and rat livers.

Methods:  The livers were haemoperfused (Hct 8.3%) via the portal vein at a constant flow. The sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre‐ (Rpre) and post‐sinusoidal (Rpost) resistances.

Results:  There was no significant difference in basal total hepatic vascular resistance (Rt) between two species, whereas Rpre in rat (69% of Rt) was significantly greater than that in guinea‐pig (61% of Rt). The responses to noradrenaline were similar; Rpre increased in a greater magnitude than Rpost, and liver weight was reduced. However, the noradrenaline‐induced increase in Rt was greater in rats than in guinea‐pigs. In contrast, histamine increased predominantly Rpost over Rpre, and increased liver weight in guinea‐pig, while it affected no haemodynamic variables in rat.

Conclusion:  There exist species differences in the hepatic vasculature between rat and guinea‐pig. Basal pre‐sinusoidal resistance in rat is greater than that in guinea‐pig. Although noradrenaline predominantly contracts pre‐sinusoidal vessels in both species, histamine causes predominant post‐sinusoidal vasoconstriction in guinea‐pig liver, while it has no vasoactive effects on rat liver.
Experimentally induced ischaemic pain in healthy humans is attenuated by the adenosine receptor antagonist theophylline
Authors: Segerdahl M. , Karelov A.
Published: December 2004

Aims:  Endogenous adenosine is considered a prominent pain mediator in ischaemia. In contrast, it has been shown that exogenous adenosine can reduce tourniquet induced ischaemic pain in healthy volunteers. The aim of this study was to investigate if pharmacological antagonism of endogenous adenosine actions with an intravenous infusion of theophylline could attenuate experimentally induced ischaemic pain.

Methods:  Nineteen healthy volunteers, 11 males, eight female, received theophylline 7 mg kg−1 or placebo intravenously, in a randomized, double blind and crossover fashion, prior to a sub‐maximum effort forearm tourniquet test. Experiments were carried out with 1‐week intervals to avoid pre‐conditioning. Pain scores [visual analogue scale (VAS), 0–100] were assessed every minute up to a maximum of 30 min.

Results:  The sum of pain scores (accumulation of VAS scores) was attenuated by theophylline, 691 [200–1550 (median and 25–75% percentiles)], compared with placebo, 1231 (545–1675), P < 0.001. Also, peak VAS pain was lower during theophylline treatment, 48 ± 38 (mean ± SD), compared with placebo, 74 ± 27, P < 0.001. Blood pressure increased during the experiment with no difference between treatments. Heart rate was not affected by tourniquet or drug treatment.

Conclusions:  It is concluded that the adenosine receptor antagonist theophylline is able to attenuate the development of ischaemia pain during experimental ischaemia in humans. This implies a role for adenosine as both facilitatory mediator and a modulator of ischaemia skeletal muscle pain.
Rapid onset of comorbidity of common mental disorders: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS)
Authors: De Graaf R. , Bijl R. V. , Ten Have M. , Beekman A. T. F. , Vollebergh W. A. M.
Published: December 2004

Objective: In a cohort of subjects with no history of psychopathology, we determined a 3‐year incidence and the risk factors of comorbid and pure mood, anxiety and substance use disorders.

Method: Data were obtained from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a longitudinal community study in which 4796 adults were interviewed in 1996, 1997 and 1999 with the Composite International Diagnostic Interview.

Results: Of 2869 cases at risk, 10.8% developed an incident disorder within 3 years, of which 16.1% was comorbid. Neuroticism, childhood trauma and parental psychiatric history were more strongly associated with comorbid than with pure disorders. No differences emerged in events occurring in the first year after baseline, but events in the period thereafter showed markedly stronger associations with comorbidity and pure mood disorder than with pure anxiety and substance use disorder. Functional disability was also linked more strongly to comorbidity and pure mood disorder.

Conclusion: Clear risk factors exist for the rapid onset of comorbidity. Interventions are needed to prevent rapid comorbidity in subjects who recently developed a primary disorder.
Lower activities of serum peptidases predict higher depressive and anxiety levels following interferon‐alpha‐based immunotherapy in patients with hepatitis C
Authors: Maes M. , Bonaccorso S.
Published: December 2004

Objective:  There is evidence that in patients with chronic hepatitis C, immunotherapy with interferon‐alpha (IFNα) may induce depression. A lowered activity of peptidases, such as prolylendopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), occurs in depression. This study examines whether lowered serum PEP or DPP IV activity before starting IFNα‐based immunotherapy predicts the increase in depressive symptoms during immunotherapy.

Method:  Serum PEP and DPP IV activities are measured in patients with hepatitis C before and 2, 4 and 16 weeks after starting IFNα‐based immunotherapy. The Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM‐A) are completed.

Results:  Patients with lower baseline PEP or DPP IV had significantly higher MADRS and HAM‐A scores both at baseline and during immunotherapy. Patients with lower baseline DPP IV had significantly higher increases in the MADRS following IFNα treatment.

Conclusion:  Lower baseline PEP and DPP IV predict higher depressive and anxiety ratings during IFNα‐based immunotherapy.
Patterns of risperidone prescription: a utilization study in south‐west France
Authors: Martin K. , Bégaud B. , Verdoux H. , Lechevallier N. , Latry P. , Moore N.
Published: December 2004

Objective:  To describe the patterns of prescriptions associated with risperidone in naturalistic clinical practice.

Method:  We analysed 500 prescription forms randomly selected from the social security insurance database in Aquitaine (south‐west France).

Results:  The prevalence of co‐prescription was 42.5% for antidepressants, 46.4% for benzodiazepines, 26.6% for other neuroleptics, 21.8% for mood stabilizers and 19% for anticholinergic drugs. The high prevalence of co‐prescribed antidepressants (59.3% Selective Serotonin Reuptake Inhibitors) may be explained by the frequent comorbidity of mood disorders in schizophrenia, and by the fact that risperidone was prescribed in naturalistic conditions in disorders other than schizophrenia.

Conclusion:  The high level of concomitant drug prescription in patients treated with risperidone illustrates the gap between clinical trials and utilization in naturalistic settings. The association antidepressant–risperidone has been insufficiently studied for efficacy or safety, and has to be explored further from both a pharmacological and clinical point of view.
Psychoeducation and cognitive‐behavioral therapy in bipolar disorder: an update
Authors: Gonzalez‐Pinto A. , Gonzalez C. , Enjuto S. , Fernandez de Corres B. , Lopez P. , Palomo J. , Gutierrez M. , Mosquera F. , Perez de Heredia J. L.
Published: December 2004

Objective:  To review the available literature on psychoeducation and cognitive‐behavioral therapy (CBT) in bipolar disorder (BD) and to give an integral view of these therapies.

Method:  Studies were identified through Medline searches in English language publications between 1971 and 2003. This was supplemented by a hand search and the inclusion of selected descriptive articles on good clinical practice.

Results:  A number of studies demonstrate that psychoeducation enhances adherence to treatment, and one finds that it improves outcome in BD. Other studies find that CBT diminishes depressive symptoms and improves quality of life in BD. Occasionally some adverse effects may occur with psychotherapy and, although they are sporadic, should not be overlooked.

Conclusion:  When combined with pharmacological treatment, psychoeducation helps to improve adherence. Training in the identification of early manic symptoms helps to improve outcomes and decreases the number of manic relapses in BD.
Time experience and time judgment in major depression, mania and healthy subjects. A controlled study of 93 subjects
Authors: Bschor T. , Ising M. , Bauer M. , Lewitzka U. , Skerstupeit M. , Müller‐Oerlinghausen B. , Baethge C.
Published: December 2004

Objective:  Studies on the time sense of depressed patients have revealed inconsistent results. Manic patients have been almost neglected.

Method:  Patients with a major depressive episode (n = 32), or a manic episode (n = 30) (both Diagnostic and Statistical Manual of Mental Disorders‐IV, Mini‐International Neuropsychiatric Interview‐confirmed), and 31 healthy controls were included. The subjective time experience was assessed by a visual analog scale (VAS), the objectively measurable time judgment abilities by the Chronotest, a computer program developed for this study, consisting of time estimation and time production tasks.

Results:  Controls reported a balanced, manic patients an enhanced, and depressive patients a slowed experience of time flow in the VAS (P < 0.001). In the time judgment tasks, however, both depressed and manic patients showed time overestimation for the longer time spans (P < 0.008).

Conclusion:  This largest study on time sense in manic patients confirmed results of a divergent alteration of time experience in depressive and in manic patients but revealed an uniform time overestimation by both patient groups in time judgment tasks.
Suitability for psychoanalytic psychotherapy: validation of the Dynamic Assessment Interview (DAI)
Authors: Valbak K. , Rosenbaum B. , Hougaard E.
Published: December 2004

Objective:  To examine the predictive validity of a particular interview and rating scale of patient suitability for psychoanalytic psychotherapy: The Dynamic Assessment Interview (DAI) scale.

Method:  Seventy‐four psychiatric out‐patients were interviewed with the DAI and the associations between DAI‐scores and measures of outcome and of therapeutic alliance were investigated.

Results:  Small to moderate correlations were found between the DAI suitability score and outcome (0.06–0.46) and between DAI suitability score and early rated alliance (0.14–0.45). The predictive value of the DAI‐score was limited although on a par with the alliance measures used in the study. No other pretherapy predictor variable investigated was found significantly to predict outcome.

Conclusion:  The predictive power of the DAI measure was limited, a result, which is in agreement with results from former studies on suitability.
Immunoglobulin G antibodies to moulds in school‐children from moisture problem schools
Authors: Taskinen T. M. , Laitinen S. , Nevalainen A. , Vepsäläinen A. , Meklin T. , Reiman M. , Korppi M. , Husman T.
Published: December 2004

Background:  The purpose of the present study was to evaluate mould‐specific immunoglobulin G (IgG) antibodies in children exposed to moisture and mould problems in their school, and the association between IgG antibodies and mould allergy, active or passive smoking and respiratory symptoms.

Methods: IgG antibodies were studied to 24 moulds in 93 children from three moisture problem schools and in 33 children from a reference school. The antibodies were measured by enzyme‐linked immunosorbent assay and compared to positive adult sera.

Results: There were no significant differences in mould‐specific IgG concentrations between exposed and non‐exposed school‐children. Antibodies to moulds common in moisture damaged buildings were associated with allergic diseases, as well as with mould‐specific immunoglobulin E (IgE) or skin prick test (SPT) findings. Aspergillus fumigatus and A. versicolor were the moulds with the most consistent findings. Active and passive smoking were associated with low levels of antibodies to many moulds. Though the association between asthma, wheezing or cough symptoms, and IgG to moulds was not significant, 7 (39%) of the 18 children with multiple (> 7) elevated IgG findings suffered from asthma or wheezing.

Conclusions: Allergy was, but asthma was not, associated with IgG antibodies to the moulds that can be found in moisture damaged buildings. However, no association was found between IgG antibodies to moulds and exposure to moisture and moulds in school.