bluuebunny/crossref_metadata_2025 huggingface dataset:
Cocaine Addicts with Conduct Disorder Are Typified by Decreased Cortisol Responsivity and High Plasma Levels of DHEA-S
Authors: Buydens-Branchey Laure , Branchey Marc
Published: July 2004

There is evidence that children with antisocial behaviors have increased plasma levels of the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) and either a decreased level of another adrenal steroid, cortisol, or a decreased cortisol responsivity to stress. Low levels of cortisol have also been reported in antisocial adults but their levels of DHEA-S have not been studied. The present study was designed to perform in adult cocaine addicts simultaneous assessments of DHEA-S and cortisol as a function of a diagnosis of antisocial personality disorder (adult symptoms) and of a retrospective diagnosis of conduct disorder (CD). Basal cortisol and DHEA-S were determined in the plasma samples of 40 hospitalized men. The patients’ cortisol responsivity was also assessed while they were being exposed to a stressful situation. Patients who had a retrospective CD diagnosis had significantly increased DHEA-S levels and secreted less cortisol when stressed. Comparisons between patients who did and did not meet the antisocial personality disorder adult criteria did not reveal any significant difference in DHEA-S or in cortisol responsivity. This could be attributed to the nature of the criteria used to define the adult disorder, which focus mostly on a failure to conform to social norms, whereas a number of CD criteria involve displays of some degree of violence. In conclusion, adults who retrospectively qualified for a CD diagnosis had increased DHEA-S levels and a decreased cortisol reactivity, confirming observations made in children and indicating that mechanisms underlying adrenal steroid alterations in childhood could still be at play in adulthood.
Treatment of Pubertal Gynecomastia with the Specific Aromatase Inhibitor Anastrozole
Authors: Riepe Felix G. , Baus Inka , Wiest Stephanie , Krone Nils , Sippell Wolfgang G. , Partsch Carl-Joachim
Published: July 2004

Gynecomastia can be detected in up to 70% of boys during puberty and in about one third of adult males. An imbalance of estrogen to androgen tissue levels is believed to be the major reason for the development of gynecomastia; as a result most medical treatments so far have tried to lower the estrogen level. Five boys with pubertal gynecomastia and breast tenderness were treated for 6 months with the selective aromatase inhibitor anastrozole. Initial plasma levels of estradiol (E2), testosterone (T), androstenedione, dehydroepiandrosterone sulfate (DHEA-S) and gonadotropins were normal. DHEA-S showed a significant rise during treatment. T and androstenedione showed no significant change during treatment. E2 decreased with therapy, although to no statistically significant extent. The E2/T ratio decreased significantly during the treatment. Breast size decreased in 4 out of 5 patients, and in 1 of these 4 boys glandular breast tissue disappeared completely. The longer the duration of gynecomastia before anastrozole administration, the smaller was the reduction of breast size. Breast tenderness was resolved in all boys within 4 weeks. No adverse effects were recorded. Since the aim of medical treatment is the total disappearance of breast tissue, anastrozole, as previous aromatase inhibitors, is of limited effect. However, anastrozole seems to be of benefit for the treatment of tenderness in gynecomastia and for patients in whom surgery is particularly risky. However, as spontaneous disappearance of pubertal gynecomastia is common, further double-blinded, placebo-controlled trials are necessary before a definite conclusion can be drawn about the effectiveness and the side effects of this therapy.
Mutations in the Lysyl Oxidase Gene Not Associated with Intracranial Aneurysm in Central European Families
Authors: Hofer Anne , Özkan Süheyla , Hermans Marcella , Kubassek Nina , Sitzer Matthias , Burtscher Johannes , Knopp Ulrich , Schoch Beate , Wanke Isabel , Huebner Felix , Raabe Andreas , Steinmetz Helmuth , Auburger Georg
Published: July 2004

Background: Lysyl oxidase is a promising candidate gene for a mutation search in intracranial aneurysm families because (a) it controls the processing, cross-linking and maturation of collagen and elastin fibers in the blood vessel wall, (b) its expression levels and activity are altered in different animal models of aneurysm pathogenesis, and (c) it is encoded within the chromosome 5q22–31 region of suggestive linkage to intracranial aneurysms. Methods: We have performed genomic sequencing of all 7 exons including the intron-exon splice sites and of the putative promoter region for lysyl oxidase in 25 patients from intracranial aneurysm multiplex families resident in Central Europe. Results: We observed 4 genetic variants including 2 novel polymorphisms, 1 in the noncoding sequence of exon 7 and the other upstream from the lysyl oxidase promoter. None of these single nucleotide polymorphisms showed an allelic association or cosegregation with intracranial aneurysm in the families. Conclusions: Genetic variants in the lysyl oxidase gene do not appear to be a major factor in the etiology of intracranial aneurysms in Central Europe.
Importance of Anatomical Asymmetries of Transverse Sinuses: An MR Venographic Study
Authors: Alper Fatih , Kantarci Mecit , Dane Senol , Gumustekin Kenan , Onbas Omer , Durur Irmak
Published: July 2004

Time-of-flight (TOF) magnetic resonance venography (MRV) is often used to examine the intracranial dural sinuses, particularly in the evaluation of dural sinus thrombosis. The goal of the study was to evaluate the use of TOF MRV in assessing the normal anatomy of dural sinuses and their variations as sources of potential pitfalls in the diagnosis of venous sinus thrombosis. Cerebral TOF MRV obtained in 105 persons with normal MR studies were reviewed to determine the presence, aplasia and hypoplasia of the transverse sinuses. Twenty-one (20%) aplasias of the left sinus, 41 (39%) hypoplasia of the left sinus, 33 (31%) symmetric, 6 (6%) hypoplasia of the right sinus, and 4 (4%) aplasias of the right sinus cases were determined in the asymmetry in sizes of transverse sinuses. These results suggested that transverse sinus flow gaps or aplasias can be observed in approximately 24% of normal population on MR imaging. The rate of these gaps in normal subjects must be kept in mind because it can be a source of misdiagnosis in cases of suspected dural sinus thrombosis.
Genetic Association of CYP46 and Risk for Alzheimer’s Disease
Authors: Combarros Onofre , Infante Jon , Llorca Javier , Berciano José
Published: July 2004

An increasing number of studies suggest that cholesterol plays an important role in regulating beta-amyloid (Aβ) metabolism in Alzheimer’s disease (AD). One of the most important mechanisms for the elimination of excess brain cholesterol is its conversion into the 24S-hydroxycholesterol catalyzed by cholesterol 24S-hydroxylase (CYP46). Preliminary evidence indicates that an intron 2 CYP46 T/C gene polymorphismis associated with increased brain Aβ load and higher risk of AD. A case-control study utilizing a clinically well-defined group of 321 sporadic AD patients and 315 control subjects was performed to test this association. Our results indicate that the intron 2 CYP46 C/C genotype may predispose to AD, and this association is independent of the apolipoprotein E genotype.
Late-Onset Depression with Mild Cognitive Deficits: Electrophysiological Evidences for a Preclinical Dementia Syndrome
Authors: Brassen Stefanie , Braus Dieter F. , Weber-Fahr Wolfgang , Tost Heike , Moritz Steffen , Adler Georg
Published: July 2004

Mild cognitive impairment (MCI) is present in up to 60% of patients with late-onset depression and constitutes a major diagnostic problem in geriatric psychiatry. Searching for sensitive markers for the detection of early brain changes suggestive of dementia, we compared this depressive risk population with mildly to moderately demented patients and cognitively unimpaired depressed patients using EEG power and coherence. We found a considerable similarity between Alzheimer’s disease patients and cognitively impaired depressed patients regarding the cognitive profile and EEG pattern. Changes in EEG power and coherence at frontotemporal leads in depressive patients with MCI thereby allowed discrimination from cognitively unimpaired patients with a sensitivity of 88% and a specifity of 81%.
Thrombin Affects Eosinophil Migration via Protease-Activated Receptor-1
Authors: Feistritzer Clemens , Mosheimer Birgit A. , Kaneider Nicole C. , Riewald Matthias , Patsch Josef R. , Wiedermann Christian J.
Published: July 2004

Background: Protease-activated receptors (PARs) are a unique class of G-protein-coupled receptors, which are activated by proteolytic cleavage of the amino terminus of the receptor itself. Although expression of the PAR1, which is typically activated by thrombin, on human eosinophils has been demonstrated, no effect of thrombin on eosinophil function has been shown yet. Thus we investigated whether thrombin affects eosinophil migration in vitro. Methods: Eosinophils were obtained from venous blood of healthy donors. Cell migration was studied by micropore filter assays. Involvement of PARs in thrombin-dependent migration was tested functionally using selective agonist peptides for PARs and a cleavage blocking PAR1 antibody. Results: Thrombin significantly stimulated eosinophil chemotaxis in a dose-dependent manner. This effect was mimicked by the PAR1 but not the PAR2 agonist and was reversed by the cleavage blocking PAR1 antibody. Checkerboard experiments indicated that eosinophil migration depends on the presence of thrombin in a concentration gradient. Conclusions: Data suggest that activation of PAR1 by thrombin stimulates directed migration of human eosinophils and thereby may affect eosinophils in tissue and allergic inflammation.
Intratracheal Instillation of Cytoplasmic Granules from Phleum pratense Pollen Induces IgE- and Cell-Mediated Responses in the Brown Norway Rat
Authors: Motta A.C. , Dormans J.A. , Peltre G. , Lacroix G. , Bois F.Y. , Steerenberg P.A.
Published: July 2004

Background: Release of cytoplasmic granules from grass pollen upon contact with water is thought to be an important source of airborne allergens. Objectives: To investigate the humoral and cellular responses to intratracheal instillation of Phleum pratense (timothy grass) pollen cytoplasmic granules (PCG) in the Brown Norway rat. Methods: PCG were purified from timothy grass pollen by filtration through 5-µm-mesh filters. Rats were sensitized (day 0) and challenged (day 21) intratracheally with purified PCG suspended in saline (6 × 106 PCG/rat). Rats were then challenged 4 weeks later (1.5 × 106 PCG/rat). Blood samples, bronchial lymph nodes and lungs were collected from the rats 4 days after the second challenge. PCG-specific IgE and IgG1 levels and specificity were determined by ELISA and Western blotting. Pollen, pollen extract and PCG-induced proliferation of lymph node cells were monitored by [3H]-thymidine incorporation in a lymph node assay. Histopathological examination was carried out on the lungs. Results: Specific IgE and IgG1 were present in the sera. Cultured lymph node cells proliferated in the presence of pollen, pollen extract and PCG. Western blots showed that all major pollen allergens are recognized by IgE and IgG1 from PCG-treated rats. Histopathological examination revealed features of a mild allergic reaction. Conclusions: In our rat model of allergy, purified timothy grass PCG instillation induced specific antibodies and lymph node cell responses, comparable to those obtained with intact pollen.
Thrombospondin-2 Is Essential for Myocardial Matrix Integrity
Authors: Schroen Blanche , Heymans Stephane , Sharma Umesh , Blankesteijn W. Matthijs , Pokharel Saraswati , Cleutjens Jack P.M. , Porter J. Gordon , Evelo Chris T.A. , Duisters Rudy , van Leeuwen Rick E.W. , Janssen Ben J.A. , Debets Jacques J.M. , Smits Jos F.M. , Daemen Mat J.A.P. , Crijns Harry J.G.M. , Bornstein Paul , Pinto Yigal M.
Published: July 2004

Cardiac hypertrophy can lead to heart failure (HF), but it is unpredictable which hypertrophied myocardium will progress to HF. We surmised that apart from hypertrophy-related genes, failure-related genes are expressed before the onset of failure, permitting molecular prediction of HF. Hearts from hypertensive homozygous renin-overexpressing (Ren-2) rats that had progressed to early HF were compared by microarray analysis to Ren-2 rats that had remained compensated. To identify which HF-related genes preceded failure, cardiac biopsy specimens were taken during compensated hypertrophy and we then monitored whether the rat progressed to HF or remained compensated. Among 48 genes overexpressed in failing hearts, we focused on thrombospondin-2 (TSP2). TSP2 was selectively overexpressed only in biopsy specimens from rats that later progressed to HF. Moreover, expression of TSP2 was increased in human hypertrophied hearts with decreased (0.19±0.01) versus normal ejection fraction (0.11±0.03 [arbitrary units];
P
<0.05). Angiotensin II induced fatal cardiac rupture in 70% of TSP2 knockout mice, with cardiac failure in the surviving mice; this was not seen in wild-type mice. In TSP2 knockout mice, angiotensin II increased matrix metalloproteinase (MMP)-2 and MMP-9 activity by 120% and 390% compared with wild-type mice (
P
<0.05). In conclusion, we identify TSP2 as a crucial regulator of the integrity of the cardiac matrix that is necessary for the myocardium to cope with increased loading and that may function by its regulation of MMP activity. This suggests that expression of TSP2 marks an early-stage molecular program that is activated uniquely in hypertrophied hearts that are prone to fail.
Bearing the 'Bare Facts' of Ritual. A Critique Of Jonathan Z. Smith's Study of the Bear Ceremony Based On a Study of the Ainu Iyomante
Authors: Kimura Takeshi
Published: July 2004

A few years ago, Benjamin Ray criticized Jonathan Z. Smith's study of the bear hunting ritual. In this article, I further examine and develop a criticism of Smith's theory of ritual. Since he presents the Ainu bear ceremony as the exemplar case and bases his theory of ritual on his interpretation of it, I review and examine the available ethnographies of the Ainu bear ceremony Iyomante . My reading of them calls into question both Smith's presentation of the ethnography of the bear ceremony and his interpretation of its meaning. Smith's focus on the ritual killing as the core of the Ainu bear ceremony as the perfect hunt to resolve incongruity between the mythical ideology and the hunting practice is based upon his not taking into consideration the Ainu religious world of meanings. From my study of the Ainu bear ceremony, I maintain that the ritual dismemberment of the bear and the ritual decoration of the bear's skull constitute the core of the meaning of the ritual. To interpret the religious meaning of this ritual, I point out the necessity for considering the Ainu view of personhood and ontological understanding of the "bear." In my interpretation of this core part of the bear ceremony, the material form, that is the bear, of the Ainu deity is ritually transformed into its spiritual mode and then sent back to the mountain whence from it originally came.
Prayer Formularies For Public Recitation. Their Use and Function in Ancient Religion
Authors: Klinghardt Matthias
Published: July 2004

In order to understand the religious mentality of ancient prayer, this article investigates the mode of public praying with respect to the use of fixed formularies, for which the most relevant references from Hellenistic and Roman antiquity are collected and presented. In spite of the different religious traditions, a surprisingly homogenous picture emerges: Public prayers had to be recited in accordance to formularies whose wording was prescribed and not at will of the praying persons. The correct recitation of a formulary (and even its proper pronunciation) was meant to guarantee the prayer's appropriateness and efficacy: an improperly recited prayer was considered to be either ineffective or even dangerous. This concept accounts for several closely related aspects which can be identified in all religious traditions: (1) Usually, the particular wording of a prayer is traced back to some divine origin which afforded its efficacy; knowledge of a prayer is, therefore, the result of revelation or of divine inspiration. (2) Correspondingly, the recitation of such formularies requires some spiritual quality of the praying person (righteousness, purity, priesthood, spiritual "ability" etc.). (3) Restriction of access to prayer formularies for certain people only is expressed by the prohibition to divulge the formulary, and by the exclusion of those considered unworthy. This picture encompasses the different religious traditions (accounting even for the "magic" prayers in the Greek magical papyri): an essential, phenomenological difference between pagan and Jewish-Christian praying cannot be substantiated. Furthermore, the concept relates to the most different hymnic genres and, therefore, can serve as the basis for a cultural comparison of ancient hymnody and for reconstructing the religious mentality of prayer.
,,Bevor einer von Jakobus kam . . .": Anmerkungen zur textkritischen und theologiegeschichtlichen Problematik von Gal 2,12
Authors: Popkes Enno Edzard
Published: July 2004

Textkritisch scheint der älteste und prominenteste Zeuge P46 die ursprüngliche Textgestalt von Gal 2,12 zu bieten. Demnach führt die paulinische Schilderung den antiochenischen Zwischenfall auf eine Einzelperson und nicht auf eine Gruppe aus dem Umfeld des Jakobus zurück (so u. a. A C D2). Anlaß für eine Korrektur bietet einerseits die uneinheitliche Textgestalt der Zeugen ℵ B D, andererseits die Divergenz von Gal 2,12 und Act 15,1.24. Die lukanische Darstellung harmonisiert das Verhältnis von Paulus, Petrus, Jakobus und Barnabas, indem zwei Konflikte ineinander projiziert werden, die im Gal chronologisch und thematisch unterschieden sind. Eine Angleichung von Gal 2,12 und Act 15,1 ist textgeschichtlich eher sekundär.
Haüyne: phase transition and high-temperature structures obtained from synchrotron radiation and Rietveld refinements
Authors: Hassan I. , Antao S. M. , Parise J. B.
Published: July 2004

The structural behaviour of a haüyne with a chemical composition of Na4.35Ca2.28K0.95[Al6Si6O24]- (SO4)2.03, at room pressure and from 33 to 1035°C on heating, was determined by using in situ synchrotron X-ray powder diffraction data (λ = 0.92249(5) Å). The satellite reflections in haüyne are lost at ∼400°C and a true substructure results because of this phase transition. There is a discontinuity in the a unit-cell parameter at ∼585°C. The α parameter increases rapidly and non-linearly to 585°C, but above 585°C, the expansion rate decreases. The percent volume change between 33 and 576°C is 2.0(3)%, and 0.6(3)% between 593 and 1035°C. Between 33 and 1035°C, the Al–O, Si–O and S–O distances are constant. Between 33 and 576°C, the angle of rotation of the AlO4 tetrahedron, jAl, changesfrom 11.5 to 5.8°, while the angle of rotation of the SiO4 tetrahedron, φSi, changesfrom 12.4 to 6.3°. The Al–O–Si bridging angle changesfrom 150.05(2) to 153.08(1)° from 33 to 576°C. Beyond 585°C, φAl and φSi angles remain nearly constant even though the maximum rotation of the tetrahedra is not achieved. Moreover, the Al–O–Si angle continues to increase at a slower rate from 585 to 1035°C by 1.05(2)°. From 33 to ∼585°C, the K atom position migrates at a slower rate than the Na and Ca atoms, and the structure expands at a high rate. Beyond 585°C, all the atomic positions of the interstitial cations (Na+, K+, Ca2+) remain nearly constant and the expansion of the structure is retarded.
The entropy of zinc chromite (ZnCr2O4)
Authors: Klemme S. , van Miltenburg J. C.
Published: July 2004

The low-temperature heat capacity of zinc chromite (ZnCr2O4) was measured between 6.5 K and 400 K using adiabatic calorimetry, and some thermochemical functions (CP(T), S(T), S°298, H(T)-H(0)) were derived from the results. The standard entropy (S°298 = 128.6±0.3 J mol-1 K-1) for zinc chromite was calculated from the results. Our calorimetric measurements indicate one extremely large anomaly in the heat capacity curve at ∼12.3 K which is related to the cubic-tetragonal transition in ZnCr2O4.
Rh autoantigen presentation to helper T cells in chronic lymphocytic leukemia by malignant B cells
Authors: Hall Andrew M. , Vickers Mark A. , McLeod Ewan , Barker Robert N.
Published: July 2004

Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune diseases directed against constituents of the blood, including hemolytic anemia (AIHA). We hypothesized that CLL cells predispose to hematologic autoimmunity by acting as aberrant antigen-presenting cells (APCs). Initially, it was confirmed that all studied patients with AIHA secondary to CLL harbored activated helper T (TH) cells specific for epitopes on the dominant red blood cell (RBC) autoantigens in primary AIHA, the Rh proteins. Rh-specific TH cells were also detected in a number of patients with CLL who, although they did not have AIHA, had low levels of anti-RBC antibody in their sera. Fractionation of putative APC populations from the peripheral blood of patients by negative selection showed that CD5+ CLL cells are the most effective cell type in processing and presenting purified Rh protein to autoreactive TH cells. This ability was confirmed using positively selected CD5+ CLL cells. Thus, our study provides the first evidence for malignant cells driving an autoimmune response by acting as aberrant APCs.
SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells
Authors: De Falco Elena , Porcelli Daniele , Torella Anna Rita , Straino Stefania , Iachininoto Maria Grazia , Orlandi Alessia , Truffa Silvia , Biglioli Paolo , Napolitano Monica , Capogrossi Maurizio C. , Pesce Maurizio
Published: July 2004

Chemokine stromal derived factor 1 (SDF-1) is involved in trafficking of hematopoietic stem cells (HSCs) from the bone marrow (BM) to peripheral blood (PB) and has been found to enhance postischemia angiogenesis. This study was aimed at investigating whether SDF-1 plays a role in differentiation of BM-derived c-kit+ stem cells into endothelial progenitor cells (EPCs) and in ischemia-induced trafficking of stem cells from PB to ischemic tissues. We found that SDF-1 enhanced EPC number by promoting α2, α4, and α5 integrin–mediated adhesion to fibronectin and collagen I. EPC differentiation was reduced in mitogen-stimulated c-kit+ cells, while cytokine withdrawal or the overexpression of the cyclin–dependent kinase (CDK) inhibitor p16INK4 restored such differentiation, suggesting a link between control of cell cycle and EPC differentiation. We also analyzed the time course of SDF-1 expression in a mouse model of hind-limb ischemia. Shortly after femoral artery dissection, plasma SDF-1 levels were up-regulated, while SDF-1 expression in the bone marrow was down-regulated in a timely fashion with the increase in the percentage of PB progenitor cells. An increase in ischemic tissue expression of SDF-1 at RNA and protein level was also observed. Finally, using an in vivo assay such as injection of matrigel plugs, we found that SDF-1 improves formation of tubulelike structures by coinjected c-kit+ cells. Our findings unravel a function for SDF-1 in increase of EPC number and formation of vascular structures by bone marrow progenitor cells.
A computer simulation analysis of the accuracy of partial genome sequencing and restriction fragment analysis in estimating genetic relationships: an application to papillomavirus DNA sequences
Authors: Qiao Baozhen , Weigel Ronald M
Published: July 2004

Background

Determination of genetic relatedness among microorganisms provides information necessary for making inferences regarding phylogeny. However, there is little information available on how well the genetic relationships inferred from different genotyping methods agree with true genetic relationships. In this report, two genotyping methods – restriction fragment analysis (RFA) and partial genome DNA sequencing – were each compared to complete DNA sequencing as the definitive standard for classification.

Results

Using the Genbank database, 16 different types or subtypes of papillomavirus were selected as study samples, because numerous complete genome sequences were available. RFA was achieved by computer-simulated digestion. The genetic similarity of samples, based on RFA, was determined from the proportion of fragments that matched in size. DNA sequences of four specific genes (E1, E6, E7, and L1), representing partial genome sequencing, were also selected for comparison to complete genome sequencing. Laboratory error was not taken into account. Evaluation of the correlation between genetic similarity matrices (Mantel's r) and comparisons of the structure of the derived dendrograms (partition metric) indicated that partial genome sequencing (for single genes) had higher agreement with complete genome sequencing, achieving a maximum Mantel's r = 0.97 and a minimum partition metric = 10. RFA had lower agreement, with a maximum Mantel's r = 0.60 and a minimum partition metric = 18.

Conclusions

This simulation indicated that for smaller genomes, such as papillomavirus, partial genome sequencing is superior to restriction fragment analysis in representing genetic relatedness among isolates. The generalizability of these results to larger genomes, as well as the impact of laboratory error, remains to be demonstrated.
The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse
Authors: Craig Cohen J , Lundblad Lennart KA , Bates Jason HT , Levitzky Michael , Larson Janet E
Published: July 2004

Background

Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype.

Results

Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations.

Conclusions

In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung.
Use and comparison of different internal ribosomal entry sites (IRES) in tricistronic retroviral vectors
Authors: Douin Victorine , Bornes Stephanie , Creancier Laurent , Rochaix Philippe , Favre Gilles , Prats Anne-Catherine , Couderc Bettina
Published: July 2004

Background

Polycistronic retroviral vectors that contain several therapeutic genes linked via internal ribosome entry sites (IRES), provide new and effective tools for the co-expression of exogenous cDNAs in clinical gene therapy protocols. For example, tricistronic retroviral vectors could be used to genetically modify antigen presenting cells, enabling them to express different co-stimulatory molecules known to enhance tumor cell immunogenicity.

Results

We have constructed and compared different retroviral vectors containing two co-stimulatory molecules (CD70, CD80) and selectable marker genes linked to different IRES sequences (IRES from EMCV, c-myc, FGF-2 and HTLV-1). The tricistronic recombinant amphotropic viruses containing the IRES from EMCV, FGF-2 or HTLV-1 were equally efficient in inducing the expression of an exogenous gene in the transduced murine or human cells, without displaying any cell type specificity. The simultaneous presence of several IRESes on the same mRNA, however, can induce the differential expression of the various cistrons. Here we show that the IRESes of HTLV-1 and EMCV interfere with the translation induced by other IRESes in mouse melanoma cells. The IRES from FGF-2 did however induce the expression of exogenous cDNA in human melanoma cells without any positive or negative regulation from the other IRESs present within the vectors. Tumor cells that were genetically modified with the tricistronic retroviral vectors, were able to induce an in vivo anti-tumor immune response in murine models.

Conclusion

Translation of the exogenous gene is directed by the IRES and its high level of expression not only depends on the type of cell that is transduced but also on the presence of other genetic elements within the vector.
Perfusion in Britain: the early days
Authors: Braimbridge Mark V
Published: July 2004

Experimental perfusion was largely the province of Germany in the nineteenth century but in the mid-twentieth century the focus of perfusion switched to the USA with the explosive clinical advances of Lillehei, Kirklin and Cooley. British clinical perfusion started with Melrose in 1953 at the Postgraduate Medical School in London but, as in other centres at that time, stopped due to the high mortality. The arrival of hands-on experience of American expertise via returning research fellows and other visitors to the USA enabled the first successful ongoing series to begin at the Hammersmith Hospital with Cleland in 1957 and then to spread around the country. The various problems of those early 1950s days are described in the units starting then.
The potential for biosensors in cardiac surgery
Authors: Connolly Patricia
Published: July 2004

Biosensor technology has been used in portable medical diagnostic instrumentation since the 1980s, mainly for the home monitoring of blood glucose in diabetics. Numerous types of sensor have been developed and reported in the literature and instrumentation which incorporates biosensors is now available for use in the emergency rooms and intensive care units for some critical parameters. However, there are still many opportunities for the development of rapid assays using biosensors which could be of assistance in cardiac surgery. This paper discusses the biosensor concept and where the key opportunities for biosensor development arise in current and future cardiac surgery.
A model for cardiopulmonary bypass redesign
Authors: Groom R C , Likosky D S , Forest R J , O’Connor G T , Morton J R , Ross C S , Clark C , Kramer R
Published: July 2004

Introduction: A portion of patients undergoing cardiac surgery may develop focal and/or subtle brain injuries secondary to cardiac surgery. There is evidence that, in some cases, these injuries may be related to cardiopulmonary bypass (CPB). Embolism and hypoperfusion are the dominant mechanisms for focal neurologic injuries among coronary artery bypass graft (CABG) surgery patients. Recent studies suggest that these mechanisms may also produce the more prevalent subtle neurological deficits. The aim of our current work is to obtain a thorough understanding of the processes of care associated with the production of embolic activity, cerebral hypoperfusion, and hemodynamic aberrations that often occur during CPB.

Methods: We developed a system for simultaneous recording of physiologic parameters, embolic activity in the CPB circuit and in the cerebral arteries, and near infrared regional cerebral oxyhemoglobin saturation (NIRS) during cardiac surgery. All data were synchronized with a video recording of the surgical procedure. Periods of embolic activity and NIRS were subsequently related to surgical and CPB processes of care through a systematic review of the patient’s surgical case video.

Results: To date, we have enrolled 47 patients undergoing coronary and/or valvular procedures. We have observed wide variation across patients in detected cerebral embolic counts, NIRS and physiologic parameters. We have identified increased embolic counts in the CPB circuit related to specific processes and events such as the method of venous drainage, the entrainment of air in the venous line, the injection of medications into the CPB circuit and blood sampling from the CPB circuit. A portion of detected changes in NIRS were related to periods of hypotension and positioning of the heart during the construction of distal coronary artery grafts on the posterior coronary artery vessels.

Summary: Use of this model provides the surgical team with detailed information regarding the contribution of CPB to the creation of precursors of neurological injury. This system provides meaningful data to guide the surgical team in the redesign of the CPB system and associated techniques.
War-related psychological stressors and risk of psychological disorders in Australian veterans of the 1991 Gulf War
Authors: Ikin Jillian F. , Sim Malcolm R. , Creamer Mark C. , Forbes Andrew B. , McKenzie Dean P. , Kelsall Helen L. , Glass Deborah C. , McFarlane Alexander C. , Abramson Michael J. , Ittak Peter , Dwyer Terry , Blizzard Leigh , Delaney Kerry R. , Horsley Keith W. A. , Harrex Warren K. , Schwarz Harry
Published: July 2004

Background

Questions remain about the long-term health impacts of the 1991 Gulf War on its veterans.

Aims

To measure psychological disorders in Australian Gulf War veterans and a military comparison group and to explore any association with exposure to Gulf War-related psychological stressors.

Method

Prevalences of DSM–IV psychological disorders were measured using the Composite International Diagnostic Interview. Gulf War-related psychological stressors were measured using a service experience questionnaire.

Results

A total of 31% of male Gulf War veterans and 21% of the comparison group met criteria for a DSM–IVdisorder first present in the post-Gulf War period. The veterans were at greater risk of developing post-Gulf War anxiety disorders including post-traumatic stress disorder, affective disorders and substance use disorders. The prevalence of such disorders remained elevated a decade after deployment. The findings can be explained partly as a ‘war-deployment effect‘. There was a strong dose–response relationship between psychological disorders and number of reported Gulf War-related psychological stressors.

Conclusions

Service in the 1991 Gulf War is associated with increased risk of psychological disorders and these are related to stressful experiences.
Behavioural interventions in the rehabilitation of acute v. chronic non-organic (conversion/factitious) motor disorders
Authors: Shapiro Allan P. , Teasell Robert W.
Published: July 2004

Background

Repeated case series have documented the effectiveness of multidisciplinary in-patient behavioural treatment for conversion disorders. However, in the absence of controlled research, treatment success could be attributed to providing patients with a face-saving opportunity to get better.

Aims

The present study contrasts two behavioural treatments to elucidate the factors underlying successful in-patient rehabilitation of this population.

Method

Thirty-nine patients underwent a standard behavioural programme. Using a crossover design, patients who did not improve underwent a strategic-behavioural treatment in which they and their families were told that full recovery constituted proof of an organic aetiology whereas failure to recover was definitive proof of a psychiatric aetiology.

Results

Chart review indicated that the standard behavioural treatment was effective for 8/9 ‘acute’ patients but only for 1/28 ‘chronic’ patients. Of the 21 patients with chronic motor disorder who then under went the strategic-behavioural intervention, 13 were symptom-free at discharge.

Conclusions

The strategic intervention was superior to standard behavioural treatment for patients with chronic motor disorder. Treatment components previously deemed critical for the effectiveness of behavioural treatment may be unnecessary.
Systematic assessments of need and care planning in severe mental illness
Authors: Marshall M. , Lockwood A. , Green G. , Zajac-Roles G. , Roberts C. , Harrison G.
Published: July 2004

Background

Surveys have shown high levels of unmet need in representative samples of people with severe mental illness. Introducing standardised needs assessment into the care planning process might reduce these needs and improve outcome.

Aims

To determine whether feedback from a standardised assessment of need enhances the effectiveness of care planning and whether exposing care coordinators to feedback on some patients improves their care of other patients.

Method

A single-blind, cluster-randomised trial involving a within-cluster individually randomised arm: patients' needs were evaluated using the Cardinal Needs Schedule and the findings were fed back to their care coordinators under the care programme approach. Atotal of 304 patients were recruited from 72 care coordinators and 242 patients (79.6%) were reassessed at 12 months.

Results

The only significant effect of the intervention was on patient satisfaction. Patients cluster-randomised to receive feedback were more satisfied than controls, but patients individually randomised to receive feedback were not.

Conclusions

Standardised needs assessment did not substantially enhance care planning in this trial. However, giving care coordinators some experience of feedback from a standardised assessment of need could improve satisfaction.
Social cognition and face processing in schizophrenia
Authors: Hall Jeremy , Harris Jonathan M. , Sprengelmeyer Reiner , Sprengelmeyer Anke , Young Andrew W. , Santos Isabel M. , Johnstone Eve C. , Lawrie Stephen M.
Published: July 2004

Studies of face processing have begun to elucidate the brain regions involved in social cognition, which include frontal and temporal regions known to be reduced in volume in schizophrenia. In this case-control study participants with schizophrenia (n=20) showed marked deficits in their ability to interpret social cues from faces, and those experiencing positive symptoms were impaired in recognising even basic facial emotions.
Impact of stressful life events, familial loading and their interaction on the onset of mood disorders
Authors: Hillegers Manon H. J. , Burger Hubert , Wals Marjolein , Reichart Catrien G. , Verhulst Frank C. , Nolen Willem A. , Ormel Johan
Published: July 2004

Background

Stressful life events are established as risk factors for the onset of mood disorders, but few studies have investigated their impact on the development of mood disorders in adolescents.

Aims

To study the effect of life events on the development of mood disorders in the offspring of parents with bipolar disorder, with respect to the possibility of a decay effect and modification by familial loading.

Method

In a high-risk cohort of 140 Dutch adolescent offspring of parents with bipolar disorder, we assessed life events, current and past DSM–IV diagnoses and familial loading. To explore their interaction and impact on mood disorder onset, we constructed four different models and used a multivariate survival analysis with time-dependent covariates.

Results

The relationship between life events and mood disorder was described optimally with a model in which the effects of life events gradually decayed by 25% per year. The effect of life event load was not significantly stronger in the case of high familial loading.

Conclusions

Independent of familial loading, life events increase the liability to mood disorders in children of patients with bipolar disorder but the effects slowly diminish with time.
Psychiatry in the future
Authors: Holloway Frank
Published: July 2004

In an era of evidence-based medicine, policy-makers and researchers are preoccupied by the task of ensuring that advances in research are implemented in routine clinical practice. This preoccupation has spawned a small but growing research industry of its own, with the development of resources such as the Cochrane Collaboration database and journals such as Evidence-Based Mental Health. In this paper, I adopt a philosophically quite unfashionable methodology – introspection – to address the question: how has research affected my practice?
Ethics and psychiatric genetics: is it ethical to test for ‘depression genes’?
Authors: Wallace John
Published: July 2004

Only one fact is certain about the future of genetic research: it will continue to raise ethical challenges for scientists, research participants, clinicians and patients (Faraone et al, 1999). Ethical issues are of concern in all branches of medicine and genetics, but they are of particular concern in the field of psychiatric genetics. This is because of the special nature of psychiatry, and its position at the intersection of the disciplines of psychology, sociology and medicine. The concern is also related to the perceived subject matter of psychiatry: the core thoughts, feelings and emotions by which we define ourselves as human beings. Many are perturbed by the idea that modifying genes could modify these features. By ‘interfering’ with our genetic heritage, it is perceived that our essential humanity is coming under threat, and the possible outcomes of this interference are worryingly unknown.
Air travel by passengers with mental disorder
Authors: Gordon Harvey , Kingham Mike , Goodwin Tony
Published: July 2004

Air travel is a rapid and efficient mode of travel nationally and internationally. People with a psychiatric disorder can usually travel safely, but may at times require an escort. People whose mental state or behaviour are disturbed are not fit to travel until stability has been achieved. Suicidal or homicidal behaviour by those so disposed are fortunately rare, but can be catastrophic in outcome. Careful assessment is necessary, and psychiatrists are advised to be more aware of the possibility of liaison with airport medical services when appropriate.
Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up
Authors: Psyrri A. , Kwong M. , DiStasio S. , Lekakis L. , Kassar M. , Sasaki C. , Wilson L.D. , Haffty B.G. , Son Y.H. , Ross D.A. , Weinberger P.M. , Chung G.G. , Zelterman D. , Burtness B.A. , Cooper D.L.
Published: July 2004

Purpose

The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors.

Patients and Methods

Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy.

Results

Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment.

Conclusion

Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.
Review of Determinants of Patients’ Preferences for Adjuvant Therapy in Cancer
Authors: Jansen Sylvia J.T. , Otten Wilma , Stiggelbout Anne M.
Published: July 2004

Purpose

Many studies have determined cancer patients’ preferences for adjuvant therapy, for example, by asking patients the extent of benefit they would need in order to accept the therapy. However, little is known about the determinants that influence these preferences. Our research goal was to explore which determinants underlie patients’ preferences by means of a literature review.

Methods

PubMed searches were conducted to identify studies in which cancer patients’ preferences for adjuvant therapy had been elicited by means of a treatment preference instrument. Twenty-three papers were evaluated with regard to reported relationships between preferences and potential determinants. A total of 40 determinants were recorded and classified into one of seven categories: (1) treatment-related determinants, (2) sociodemographic characteristics and current quality of life, (3) clinical characteristics, (4) measurement instrument-related determinants, (5) time-related determinants, (6) cognitive/affective determinants, and (7) specialist-related determinants.

Results

The benefit and toxicity of treatment, experience of the treatment, and having dependents (eg, children) living at home were important determinants of patients’ preferences. Furthermore, qualitative data suggested that cognitive/affective and specialist-related determinants might have a large impact on patients’ treatment preferences.

Conclusion

Our results show that patients’ preferences cannot fully be explained on the basis of treatment-related determinants and patient and clinical characteristics. More research is needed in the area of cognitive/affective and specialist-related determinants because of the lack of quantitative results. Furthermore, we recommend carrying out larger studies in which the (internal) relationships between determinants and preferences are assessed in the context of a cognitive cost-benefit model.