bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sustainable Forestry Initiatives impact on stumpage markets in the US South
Authors: Brown Roger , Zhang Daowei
Published: October 2005

Using survey data and an equilibrium displacement model, we estimate the market and economic impacts of the American Forest and Paper Association's Sustainable Forestry Initiative (SFI) on stumpage markets in the US South. We examine four timber product markets: softwood pulpwood, softwood sawtimber, hardwood pulpwood, and hardwood sawtimber. In each market we calculate changes in producer and consumer welfare using the equilibrium displacement model that accounts for reductions in timber inventories caused by SFI compliance. We find that SFI compliance costs the US South's economy about $36 million annually. SFI-compliant stumpage producers lose more than $33 million each year in producer surplus as a result of SFI compliance, and consumers lose about $12 million annually in consumer surplus due to higher product prices. These costs are offset partially by benefits to nonindustrial private forest producers, non-SFI-compliant industry producers, and public forest producers, who collectively gain about $10 million in producer surplus annually as a result of higher stumpage prices.
Soil properties, aspen, and white spruce responses 5 years after organic matter removal and compaction treatments
Authors: Kabzems Richard , Haeussler Sybille
Published: October 2005

Retaining organic matter and preventing soil compaction are important factors affecting the sustainability of managed forests. To assess how these factors affect short-term ecosystem dynamics, pre-treatment and 1 year and 5 year post-treatment soil properties and post-treatment tree growth responses were examined in a boreal trembling aspen (Populus tremuloides Michx.) dominated ecosystem in northeastern British Columbia, Canada. The experiment used a completely randomized design with three levels of organic matter removal (tree stems only; stems and slash; stems, slash, and forest floor) and three levels of soil compaction (none, intermediate (2-cm impression), heavy (5-cm impression)). Removal of the forest floor initially stimulated aspen regeneration and significantly reduced height growth of aspen and white spruce (Picea glauca (Moench) Voss). The compaction treatments had no effect on aspen regeneration density. At year 5, heights of both aspen and white spruce were negatively correlated (r2 > 0.31, p < 0.0001) with upper mineral soil bulk density and were lowest on forest floor removal treatments, where minimal recovery from compaction was observed. There was some evidence for recovery of soil properties to preharvest conditions where expansion of herbaceous vegetation increased soil organic matter.
MAXIMIZING A VORONOI REGION: THE CONVEX CASE
Authors: DEHNE FRANK , KLEIN ROLF , SEIDEL RAIMUND
Published: October 2005

Given a set S of s points in the plane, where do we place a new point, p, in order to maximize the area of its region in the Voronoi diagram of S and p? We study the case where the Voronoi neighbors of p are in convex position, and prove that there is at most one local maximum.
DIFFERENTIAL TOPOLOGY AND GEOMETRY OF SMOOTH EMBEDDED SURFACES: SELECTED TOPICS
Authors: CAZALS FRÉDÉRIC , POUGET MARC
Published: October 2005

The understanding of surfaces embedded in E3 requires local and global concepts, which are respectively evocative of differential geometry and differential topology. While the local theory has been classical for decades, global objects such as the foliations defined by the lines of curvature, or the medial axis still pose challenging mathematical problems. This duality is also tangible from a practical perspective, since algorithms manipulating sampled smooth surfaces (meshes or point clouds) are more developed in the local than the global category. As a prerequisite for those interested in the development of algorithms for the manipulation of surfaces, we propose a concise overview of core concepts from differential topology applied to smooth embedded surfaces.

We first recall the classification of umbilics, of curvature lines, and describe the corresponding stable foliations. Next, fundamentals of contact and singularity theory are recalled, together with the classification of points induced by the contact of the surface with a sphere. This classification is further used to define ridges and their properties, and to recall the stratification properties of the medial axis. Finally, properties of the medial axis are used to present sufficient conditions ensuring that two embedded surfaces are ambient isotopic.

From a theoretical perspective, we expect this survey to ease the access to intricate notions scattered over several sources. From a practical standpoint, we hope it will be useful for those interested in certified approximations of smooth surfaces.
(DIS)BELIEF CHANGE AND ARGUED FEED-BACK DIALOG
Authors: PERRUSSEL LAURENT , THÉVENIN JEAN-MARC
Published: October 2005

This paper focuses on the features of belief change in a multi-agent context where agents consider beliefs and disbeliefs. Disbeliefs represent explicit ignorance and are useful to prevent agents to entail conclusions due to their ignorance. Agents receive messages holding information from other agents and change their belief state accordingly. An agent may refuse to adopt incoming information if it prefers its own (dis)beliefs. For this, each agent maintains a preference relation over its own beliefs and disbeliefs in order to decide if it accepts or rejects incoming information whenever inconsistencies occur. This preference relation may be built by considering several criteria such as the reliability of the sender of statements or temporal aspects. This process leads to non-prioritized belief revision.

In this context we first present the * and − operators which allow an agent to revise, respectively contract, its belief state in a non-prioritized way when it receives an incoming belief, respectively disbelief. We show that these operators behave properly. Based on this we then illustrate how the receiver and the sender may argue when the incoming (dis)belief is refused. We describe pieces of dialog where (i) the sender tries to convince the receiver by sending arguments in favor of the original (dis)belief and (ii) the receiver justifies its refusal by sending arguments against the original (dis)belief. We show that the notion of acceptability of these arguments can be represented in a simple way by using the non-prioritized change operators * and −. The advantage of argumentation dialogs is twofold. First whenever arguments are acceptable the sender or the receiver reconsider its belief state; the main result is an improvement of the reconsidered belief state. Second the sender may not be aware of some sets of rules which act as constraints to reach a specific conclusion and discover them through argumentation dialogs.
GLOBAL PROPAGATION IN BAYESIAN NETWORKS VS SEMIJOIN PROGRAMS IN RELATIONAL DATABASES
Authors: WU DAN , WONG MICHAEL
Published: October 2005

Bayesian networks have been well established as an effective framework for uncertainty management using probability. Various methods for probabilistic reasoning in Bayesian networks have been developed and matured. Recently, research has shown that there exists an intriguing relationship between Bayesian networks and relational databases. Adding to that intriguing relationship, in this paper, we reveal that the global propagation method for probabilistic reasoning in Bayesian networks has a close tie with the well known semijoin programs for query answering in relational databases. This linkage between these two apparently different but closely related knowledge representations suggests that well developed techniques for query answering in relational databases could be applied to probabilistic reasoning in Bayesian networks for large and complex domains.
Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage
Authors: O’Donnell J. Michael , Zampino Manuela , Alpert Nathaniel M. , Fasano Matthew J. , Geenen David L. , Lewandowski E.Douglas
Published: October 2005

Triacylglycerol (TAG) storage and turnover rates in the intact, beating rat heart were determined for the first time using dynamic mode13C- NMR spectroscopy to elucidate profound differences between hearts from diabetic rats (DR, streptozotocin treatment) and normal rats (NR). The incorporation of [2,4,6,8,10,12,14,16-13C8]palmitate into the TAG pool was monitored in isolated hearts perfused with physiological (0.5 mM palmitate, 5 mM glucose) and elevated substrate levels (1.2 mM palmitate, 11 mM glucose) characteristic of the diabetic condition. Surprisingly, although the normal hearts were enriched at a near-linear profile for ≥2 h before exponential characterization, exponential enrichment of TAG in diabetic hearts reached steady state after only 45 min. Consequently, TAG turnover rate was determined by fitting an exponential model to enrichment data rather than conventional two-point linear analysis. In the high-substrate group, both turnover rate (DR 820 ± 330, NR 190 ± 150 nmol·min−1·g−1dry wt; P < 0.001) and [TAG] content (DR 78 ± 10, NR 32 ± 4 μmol/g dry wt; P < 0.001) were greater in the diabetic group. At lower substrate concentrations, turnover was greater in diabetics (DR 530 ± 300, NR 160 ± 30; P < 0.05). However, this could not be explained by simple mass action, because [TAG] content was similar between groups [DR 34 ± 7, NR 39 ± 9 μmol/g dry wt; not significant (NS)]. Consistent with exponential enrichment data,13C fractional enrichment of TAG was lower in diabetics (low- substrate groups: DR 4 ± 1%, NR 10 ± 4%, P < 0.05; high-substrate groups: DR 8 ± 3%, NR 14 ± 9%, NS), thereby supporting earlier speculation that TAG is compartmentalized in the diabetic heart.
Glucose induces increases in levels of the transcriptional repressor Id2 via the hexosamine pathway
Authors: Grønning Line Mariann , Tingsabadh Rommaneeya , Hardy Kristine , Dalen Knut Thomas , Jat Parmjit S. , Gnudi Luigi , Shepherd Peter R.
Published: October 2005

Changes in glucose levels are known to directly alter gene expression. A number of previous studies have found that these effects are in part mediated by modulating the levels and the activity of transcription factors. We have investigated an alternative mechanism by which glucose might regulate gene expression by modulating levels of a transcriptional repressor. We have focused on Id2, which is a protein that indirectly regulates gene expression by sequestering certain transcription factors and preventing them from forming functional dimers. Id2 targets include the class A basic helix-loop-helix transcription factors and the sterol regulatory element-binding protein (SREBP)-1. We demonstrate that increases in glucose levels cause a rapid increase in levels of Id2 in J774.2 macrophages, and a number of lines of evidence indicate that this is via the hexosamine pathway because 1) the effect of glucose requires glutamine; 2) the effect of glucose is mimicked by low levels of glucosamine; 3) the effect of glucose is inhibited by azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase (GFAT); and 4) adenoviral mediated overexpression of GFAT increases levels of Id2. We go on to show that increases in Id2 can have functional effects on metabolic genes, because Id2 blocked the SREBP-1-induced induction of hormone-sensitive lipase (HSL) promoter activity, whereas Id2 alone does not modulate activity of the HSL promoter. In summary, these studies define a new mechanism by which glucose uses the hexosamine pathway to regulate gene expression by increasing levels of a transcriptional repressor.
Increased malonyl-CoA and diacylglycerol content and reduced AMPK activity accompany insulin resistance induced by glucose infusion in muscle and liver of rats
Authors: Kraegen Edward W. , Saha Asish K. , Preston Elaine , Wilks Donna , Hoy Andrew J. , Cooney Gregory J. , Ruderman Neil B.
Published: October 2005

Glucose infusion in rats for 1–4 days results in insulin resistance and increased triglyceride, whole tissue long-chain fatty acyl-CoA (LCA-CoA), and malonyl-CoA content in red skeletal muscle. Despite this, the relation between these alterations and the onset of insulin resistance has not been defined. We aimed to 1) identify whether the changes in these lipids and of diacylglycerol (DAG) precede or accompany the onset of insulin resistance in glucose-infused rats, 2) determine whether the insulin resistance is associated with alterations in AMP-activated protein kinase (AMPK), and 3) assess whether similar changes occur in liver and in muscle. Hyperglycemia (17–18 mM) was maintained by intravenous glucose infusion in rats for 3 or 5 h; then euglycemia was restored and a 2-h hyperinsulinemic clamp was performed. Significant ( P < 0.01) muscle and liver insulin resistance first appeared in red quadriceps and liver of the glucose-infused group at 5 h and was associated with a twofold increase in DAG and malonyl-CoA content and a 50% decrease in AMPK and acetyl-CoA carboxylase (ACC) phosphorylation and AMPK activity. White quadriceps showed qualitatively similar changes but without decreases in AMPK or ACC phosphorylation. Triglyceride mass was increased at 5 h only in liver, and whole tissue LCA-CoA content was not increased in liver or either muscle type. We conclude that the onset of insulin resistance induced by glucose oversupply correlates temporally with increases in malonyl-CoA and DAG content in all three tissues and with reduced AMPK phosphorylation and activity in red muscle and liver. In contrast, it was not associated with increased whole tissue LCA-CoA content in any tissue or triglyceride in muscle, although both are observed at later times.
Increased mitochondrial glycerol-3-phosphate acyltransferase protein and enzyme activity in rat epididymal fat upon cessation of wheel running
Authors: Kump David S. , Laye Matthew J. , Booth Frank W.
Published: October 2005

Triacylglycerol synthesis in rat epididymal fat overshoots sedentary levels at 10, 29, and 53 h of physical inactivity after 21 days of wheel running. The purposes of the present study were to determine 1) whether this effect is also observed after an acute bout of physical activity and 2) what enzymatic changes might contribute to this effect. We show that more than one bout of physical activity, such as that which occurs with 21 days of wheel running, is necessary for palmitic acid incorporation into triacylglyceride (triglyceride synthesis) to overshoot sedentary values, which suggests that pretranslational mechanisms may be responsible for this overshoot effect. Ten hours after 21 days of wheel running, activity of the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform, a key regulator of triacylglycerol synthesis, overshot sedentary values by 48% and remained higher than sedentary values at 29 and 53 h of reduced physical activity. The overshoot in mtGPAT1 activity was accompanied by an increase in mtGPAT protein level. Cyclic AMP response element-binding protein-binding protein level was higher in sedentary 29 h after 21 days of wheel running. AMP kinase-α Thr172phosphorylation was increased immediately after treadmill running, but decreased to sedentary values by 5 h after activity. Casein kinase-2α protein level and activity were unchanged. We conclude that an increase in mtGPAT protein might contribute to the overshoot in triacylglycerol synthesis.
Adenosine inhibits ENaC via cytochromeP-450 epoxygenase-dependent metabolites of arachidonic acid
Authors: Wei Yuan , Sun Peng , Wang ZhiJian , Yang BaoFeng , Carroll Mairead A. , Wang Wen-Hui
Published: October 2005

We used the patch-clamp technique to examine the effect of adenosine on epithelial sodium channel (ENaC) activity in rat cortical collecting duct (CCD). Application of adenosine inhibits ENaC activity, and the effect of adenosine was mimicked by cyclohexyladenosine (CHA), an A1adenosine-receptor agonist that reduced channel activity from 1.32 to 0.64. The inhibitory effect of CHA on ENaC was mimicked by cyclopentyladenosine (CPA), which reduced channel activity from 1.1 to 0.55. In contrast, application of CGS-21680, an A2aadenosine-receptor agonist, had no effect on ENaC and increased channel activity from 0.96 to 1.22. This suggests that the inhibitory effect of adenosine analogs resulted from stimulation of the A1adenosine receptor. Inhibition of PLC with U-73122 failed to abolish the effect of CHA on ENaC. In contrast, the inhibitory effect of CHA on ENaC was absent in the presence of the PLA2inhibitor arachidonyl trifluoromethyl ketone (AACOCF3). This suggests a role of arachidonic acid (AA) in mediating the effect of adenosine on ENaC. To determine the metabolic pathway of AA responsible for the effect of adenosine, we examined the effect of CHA in the presence of indomethacin or N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH). Inhibition of cytochrome P-450 (CYP) epoxygenase with MS-PPOH blocked the effect of CHA on ENaC. In contrast, CHA reduced ENaC activity in the presence of indomethacin. This suggests that CYP epoxygenase-dependent metabolites of AA mediate the effect of adenosine. Because 11,12-epoxyeicosatrienoic acid (11,12-EET) inhibits ENaC activity in the CCD (Wei Y, Lin DH, Kemp R, Yaddanapudi GSS, Nasjletti A, Falck JR, and Wang WH. J Gen Physiol 124: 719–727, 2004), we examined the role of 11,12-EET in mediating the effect of adenosine on ENaC. Addition of 11,12-EET inhibited ENaC channels in the CCD in which adenosine-induced inhibition was blocked by AACOCF3. We conclude that adenosine inhibits ENaC activity by stimulation of the A1adenosine receptor in the CCD and that the effect of adenosine is mediated by 11,12-EET.
Effect of peristaltic contractions of the renal pelvic wall on solute concentrations of the renal inner medulla in the hamster
Authors: Pruitt Mary Ella C. , Knepper Mark A. , Graves Bruce , Schmidt-Nielsen Bodil
Published: October 2005

The mechanism of solute accumulation in the renal inner medulla remains an unresolved issue. Experiments were carried out in hamsters to address the possibility that the peristaltic contractions of the renal pelvic wall surrounding the inner medulla play a role in the inner medullary concentrating process. The right renal pelvis was subjected to one of four manipulations (surgical removal of the pelvic wall, paralysis of the pelvic wall with xylocaine, inhibition of pelvic contractions by direct application of heat, or sham treatment) followed by analysis of the inner medullary solute concentrations in the right kidney vs. the untouched left kidney. Removal of the pelvic wall resulted in a marked reduction in inner medullary osmolality, confirming prior observations. Paralysis of the pelvic wall with xylocaine produced a similar decrease in inner medullary osmolality, despite the fact that urine flow was maintained. In contrast, sham treatment (surgical exposure of the right renal pelvic wall without any further manipulation) did not decrease inner medullary osmolality. To test whether the decrease in urinary osmolality following xylocaine treatment could have been due to a side effect of the drug, pelvic peristaltic contractions were eliminated in another way, by direct application of heat to denature the smooth muscle of the pelvic wall. This procedure also significantly decreased inner medullary osmolality. We conclude that elimination of the contractions of the renal pelvic wall in the hamster significantly impairs inner medullary concentrating ability.
Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cyrat kidneys
Authors: Warford-Woolgar Lori , Peng Claudia Yu-Chen , Shuhyta Jamie , Wakefield Andrew , Sankaran Deepa , Ogborn Malcolm , Aukema Harold M.
Published: October 2005

Renal prostanoids are important regulators of normal renal function and maintenance of renal homeostasis. In diseased kidneys, renal cylooxygenase (COX) expression and prostanoid formation are altered. With the use of the Han:Sprague-Dawley- cy rat, the aim of this study was to determine the relative contribution of renal COX isoforms (protein, gene expression, and activity) on renal prostanoid production [thromboxane B2(TXB2, stable metabolite of TXA2), prostaglandin E2(PGE2), and 6-keto-prostaglandin F1α(6-keto-PGF1α, stable metabolite of PGI2)] in normal and diseased kidneys. In diseased kidneys, COX-1-immunoreactive protein and mRNA levels were higher and COX-2 levels were lower compared with normal kidneys. In contrast, COX activities were higher in diseased compared with normal kidneys for both COX-1 [0.05 ± 0.02 vs. 0.45 ± 0.11 ng prostanoids·min−1·mg protein−1( P < 0.001)] and COX-2 [0.64 ± 0.10 vs. 2.32 ± 0.22 ng prostanoids·min−1·mg protein−1( P < 0.001)]. As the relative difference in activity was greater for COX-1, the ratio of COX-1/COX-2 was higher in diseased compared with normal kidneys, although the predominant activity was still due to the COX-2 isoform in both genotypes. Endogenous and steady-state in vitro levels of prostanoids were ∼2–10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB2> 6-keto-PGF1α> PGE2, as determined by higher renal prostanoid levels and COX activity ratios of TXB2/6-keto-PGF1α, TXB2/PGE2, and 6-keto-PGF1α/PGE2. This specificity in both the COX isoform type and for the prostanoids produced has implications for normal and diseased kidneys in treatments involving selective inhibition of COX isoforms.
Technological Innovations in Clinical Assessment and Psychotherapy
Authors: Emmelkamp Paul M.G.
Published: October 2005

In this paper the application of computer technology and the use of the Internet in mental health care are critically reviewed. A number of on-line screening devices have been developed for anxiety disorders, mood disorders, and substance abuse disorders, with great potential for clinical practice. On line assessment is generally equivalent to clinical assessment. A number of studies have shown that self-help treatment programmes on stand-alone computers are as effective as routine clinical care. The Internet enhances the therapeutic possibilities of computers by offering feedback of therapists and more tailor-made treatment. A number of randomized clinical trials (RCTs) have shown that Internet-based treatment is more effective than no-treatment and as effective as face-to-face treatment. Research so far has been limited to anxiety disorders, burn-out, depression, headache, insomnia, tinnitus and obesity. Further, exposure through virtual reality has been found effective in a number of RCTs in specific phobias, but results with respect to the effects of the use of virtual reality techniques to other disorders are inconclusive. It is concluded that computer-driven assessment and treatment has many advantages and few disadvantages. A number of reasons are discussed which will preclude large-scale implementation of computer-driven assessment and therapy in the near future.
Comparison of Changes in Physical Self-Concept, Global Self-Esteem, Depression and Anxiety following Two Different Psychomotor Therapy Programs in Nonpsychotic Psychiatric Inpatients
Authors: Knapen Jan , van de Vliet Peter , van Coppenolle Herman , David Ans , Peuskens Joseph , Pieters Guido , Knapen Koen
Published: October 2005

Background: The first objective of this study was to compare the changes in physical self-concept, global self-esteem, depression and anxiety after participation in one of two 16-week psychomotor therapy programs for nonpsychotic psychiatric inpatients. The second objective was to study the relationship between changes in these variables. Methods: One hundred and ninety-nine inpatients were randomly assigned to either a personalized psychomotor fitness program, consisting of aerobic exercise and weight training, or a general program of psychomotor therapy, consisting of different forms of physical exercises and relaxation training. Physical self-con cept was evaluated using the Dutch version of the Physical Self-Perception Profile at baseline, after 8 weeks, and after completion of the 16-week interventions. At the same time points, additional variables of global self-esteem, depression and anxiety were assessed by means of the Rosenberg Self-Esteem Inventory, the Beck Depression Inventory and the Trait Anxiety Inventory, respectively. Results: After 16 weeks, both groups showed significant improvements in all outcome measures (p values ranged from 0.01 to < 0.0001), with no between-group differences. In both groups, the improvement in physical self-concept was correlated with increased global self-esteem and decreased depression and anxiety levels (p < 0.01). Conclusions: The results suggest that both psychomotor therapy programs are equally effective in enhancing physical self-concept. The relationship between improvements in physical self-concept and enhancements in global self-esteem, depression and anxiety supports the potential role of the physical self-concept in the recovery process of depressed and anxious psychiatric inpatients.
Stability of Alexithymia and Its Relationships with the ‘Big Five’ Factors, Temperament, Character, and Attachment Style
Authors: Picardi Angelo , Toni Alessandro , Caroppo Emanuele
Published: October 2005

Background: Controversy still exists concerning the stability of the alexithymia construct. Also, although alexithymia has been found to be related in a theoretically meaningful way to other personality constructs such as the ‘Big Five’ factors, few studies have investigated its relationship with influential constructs such as temperament and character, and attachment security. Methods: Two hundred twenty-one undergraduate and graduate students were administered the Toronto Alexithymia Scale (TAS-20), the State-Trait Anxiety Inventory (STAI), the Zung Depression Scale (ZDS), the Temperament and Character Inventory (TCI-125), the Big Five Questionnaire (BFQ), and the Experiences in Close Relationships (ECR) questionnaire. After 1 month, 115 participants completed again the TAS-20, STAI, and ZDS. Results: Alexithymia was only moderately correlated with depression and anxiety. Both the absolute and relative stability of TAS-20 total and subscale scores was high, and a negligible portion of their change over time was accounted for by changes in depression or anxiety. In separate multiple regression models including also gender, age, depression and anxiety, TAS-20 total and subscale scores were correlated with low energy/extraversion, low emotional stability, openness, low friendliness/agreeableness; harm avoidance, low self-directedness, low cooperativeness, low reward dependence; attachment-related avoidance and anxiety. Conclusions: Our findings lend support for both absolute and relative stability of alexithymia, corroborate an association between alexithymia and insecure attachment, and contribute to a coherent placing of alexithymia in the broader theoretical network of personality constructs.
Balancing Innovation and Access to Healthcare through the Patent System – An Australian Perspective
Authors: Nicol Dianne
Published: October 2005

This article examines the enforcement of gene and other research tool patents in Australia. An empirical analysis of patenting practices in the Australian medical biotechnology industry showed heightened concern about the impact of patents on research and diagnostic testing, but provided little evidence to support these concerns at that time. Since then, the Australian company Genetic Technologies Ltd. has been enforcing its patents for non-coding DNA sequences. The governments of Australia are encouraging the biotechnology industry to better protect and enforce intellectual property rights, but recognize these needs to be balanced against access to healthcare. The article discusses proposals made by the Australian Law Reform Commission to adjust the balance, both by tightening the requirements for obtaining patents and by introducing various options to assist providers of diagnostic services and others in using patented inventions, but at the same time maintaining the incentive to innovate.
The Patent Is Political: The Consequences of Patenting the BRCA Genes in Britain
Authors: Parthasarathy Shobita
Published: October 2005

Objectives: The paper explores the attempt by an American biotechnology company, Myriad Genetics, to use its patent rights over the BRCA genes to transfer its technology of genetic testing for breast and ovarian cancer to Britain. It also investigates the responses of British scientists, health care professionals and patient advocates to this attempted technology transfer. Methods: This paper is based on approximately 100 in-depth interviews, document analysis and ethnographic observation conducted in the United States and Britain from 1998 to 2001. Results: The BRCA gene patents inspired political resistance and mobilized opposition to the patenting of genes in general. They also provided an opportunity for the British to assert their national identity as they argued that a British BRCA testing service needed to be available within the context of the National Health Service to all citizens equally. Conclusions: Patents are not only legal documents and technical descriptions, but political tools as well. As they are increasingly deemed vital to economic globalization, patents have become mobilizing tools for anti-globalization activists and non-governmental organizations from less developed countries, and for asserting local and national identities.
Feasibility of Retroviral Vector-Mediated in utero Gene Transfer to the Fetal Rabbit
Authors: Moreno Rafael , Rosal Marta , Cabero Lluis , Gratacós Eduard , Aran Josep M.
Published: October 2005

Objectives: Successful treatment or prevention of severe hereditary diseases could conceivably be achieved by genetic intervention early in development. Viral vector-mediated fetal gene transfer is proving a valuable tool to test the above concept in relevant animal models. Although the pregnant rabbit is a well-recognized model for fetal therapy, few preclinical assays have used it to validate fetal gene transfer approaches. In this preliminary study we assessed for the first time the feasibility of retroviral vector-mediated in utero gene transfer in the fetal rabbit. Methods: Different amounts of the vesicular stomatitis virus G pseudotyped MFG(nls)LacZ retroviral vector, expressing a nuclear-localized β-galactosidase reporter protein were injected intraperitoneally and -hepatically into 20- to 22-day-old fetuses. At 8–9 days post-treatment, the pups were sacrificed and the tissues harvested for analysis. Evidence of gene transfer was obtained by PCR amplification of proviral sequences within genomic DNA isolated from the treated samples. Transgenic β-galactosidase expression was assessed by X-gal histochemical staining. Results: By intraperitoneal injection 43% of the viable fetuses treated (3/7) showed evidence of successful LacZ gene transfer and low-level β-galactosidase expression into liver and heart, whereas by intrahepatic injection roughly 38% (3/8) of the livers were positive for LacZ gene transfer and expression. The success rate for the viable fetuses rose to 67% positive livers (4/6) when a near double amount of recombinant virus was injected using a 10-fold concentrated virus stock. In terms of short-term safety, fetal and maternal survival rates approached 80% of treated fetuses, and 100% of treated does. Conclusions: The pregnant rabbit is a useful and reliable model allowing the design of further studies to optimize the conditions for effective, safer, and persistent retroviral vector-mediated fetal gene transfer.
Pseudotrisomy 13: Clinical Findings and Genetic Implications
Authors: Schulz Solveig , Gerloff Claudia , Kalinski Thomas , Mawrin Christian , Kanakis Dimitrios , Haas Dorothea , Hahn Heidi , Wieacker Peter
Published: October 2005

The combination of holoprosencephaly, postaxial polydactyly, and normal karyotype has been termed pseudotrisomy 13 syndrome. Here, we report the prenatal diagnosis of pseudotrisomy 13 in three siblings suggesting autosomal recessive inheritance of this syndrome. Clinical overlap with hydrolethalus syndrome, Smith-Lemli-Opitz syndrome, Meckel syndrome, and Pallister-Hall syndrome is discussed.
Prenatal Diagnosis of a Fetal Chest Wall Cystic Lymphangioma Using Ultrasonography and MRI: A Case Report with Literature Review
Authors: Rasidaki Maria , Sifakis Stavros , Vardaki Elpida , Koumantakis Eugenios
Published: October 2005

A case of fetal chest wall cystic lymphangioma diagnosed prenatally at 28 weeks’ gestation is reported. Ultrasound examination showed a multilocular, large cystic mass (10 × 22 × 29 mm) on the left side of the fetus in the area of the lower chest and upper abdomen, without color flow imaging. Magnetic resonance imaging was used to evaluate the extent and the tissue characteristics of the lesion. Two months after birth the lymphangioma was surgically removed, following an infection and a rapid increase in size. The case is discussed, and a short review of the literature is reported.
Endothelial Nitric Oxide Synthase Polymorphism Is Not Associated with Placental Abruption in Finnish Women
Authors: Toivonen Sari , Keski-Nisula Leea , Romppanen Eeva-Liisa , Helisalmi Seppo , Punnonen Kari , Heinonen Seppo
Published: October 2005

Objective: To study whether genetic variability in the gene encoding endothelial nitric oxide synthase (eNOS) affects individual susceptibility to the development of placental abruption during pregnancy. Methods: One hundred and sixteen pregnant women with placental abruption and 113 healthy controls were genotyped for Glu298Asp polymorphism in the eNOS gene. Chi-square analysis was used to assess the differences in genotype and allele frequencies between the two groups. Results: A statistically similar allelic distribution of eNOS Glu298Asp polymorphism was observed in the two groups, with the frequency of the variant G allele being 66.8% in the abruption group and 68.1% in the control group (OR 0.94, 95% CI: 0.64–1.39; p = 0.76). The genotype distribution of the eNOS polymorphism was also found to be statistically similar (p = 0.72). Conclusions: The observed genotype data in subjects from eastern Finland suggest that the Glu298Asp polymorphism of the eNOS gene does not contribute to placental abruption in this population.
Congenital Myotonic Dystrophy
Authors: Upadhyay K. , Thomson A. , Luckas M.J.M.
Published: October 2005

We describe a case of severe congenital myotonic dystrophy (CDM). A 38-year-old primigravida, who was known to suffer from mild myotonic dystrophy (DM), conceived spontaneously and booked for confinement at 11 weeks in our unit. The couple had been fully counseled about the risks of transmission of this condition to their offspring before embarking on this pregnancy. Despite being fully aware of the risks, they declined prenatal diagnosis. The pregnancy was monitored by serial ultrasound scans. The diagnosis of CDM was suspected by ultrasound markers of borderline ventriculomegaly, polyhydramnios, and reduced fetal movements. The pregnancy ended prematurely at 33 weeks in an emergency caesarean section because of severe fetal compromise. The neonate died almost immediately after birth. The genetic analysis of cord blood confirmed severe DM. This case highlights the importance of ultrasound markers for the diagnosis of CDM in the absence of definitive prenatal diagnosis.
Fetal MRI of a Severe Dandy-Walker Malformation with an Enlarged Posterior Fossa Cyst Causing Severe Hydrocephalus
Authors: Teksam Mehmet , Ozyer Umut , McKinney Alexander , Kirbas Ismail , Cakir Banu
Published: October 2005

We present a case of severe Dandy-Walker malformation with enlarged posterior fossa cyst extruding through the incisura of the tentorium and causing severe hydrocephalus. A posterior fossa malformation was suspected by ultrasonography and was further evaluated by fetal magnetic resonance imaging (MRI). Fetal MRI demonstrated that there were no associated anomalies and the decision was made to continue with labor instead of terminating the pregnancy. The precise diagnosis and absence of associated anomalies revealed by MRI aided in parent counseling and obstetrical management.
Rare Case of Exomphalos Complicated with Umbilical Cord Teratoma in a Fetus with Trisomy 13
Authors: Hargitai B. , Csabai L. , Bán Z. , Hetényi I. , Szűcs I. , Varga S. , Papp Z.
Published: October 2005

An exomphalos containing unusual solid and cystic mass was diagnosed during a routine ultrasound examination in the 17th week of gestation. Further investigations were planned but the pregnancy was terminated. The fetopathological examination revealed an umbilical cord teratoma. Although this entity is very rare it should be emphasized as a possible differential diagnosis when cystic lesion of the cord is detected. Large teratomas associated with abdominal wall defect may have poor fetal outcome and can be associated with structural and chromosomal abnormalities. In our case trisomy 13 was diagnosed.
Effects of Ibuprofen and Indomethacin on Urinary Antidiuretic Hormone Excretion in Preterm Infants Treated for Patent Ductus Arteriosus
Authors: Zanardo Vincenzo , Vedovato Stefania , Lago Paola , Piva Daniele , Faggian Diego , Chiozza Laura
Published: October 2005

Objective: To compare the effects of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on urinary antidiuretic hormone (ADH) excretion, as a cause of oliguria. Study Design: Forty-four respiratory distress syndrome prematures (≤34 weeks’ gestation) with PDA received either ibuprofen (n = 22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or three doses at 12-hour intervals of indomethacin (n = 24), 0.2 mg/kg, both infused continuously over a period of 15 min. Urinary ADH excretion, diuresis, serum creatinine, urinary sodium, fractional excretion of sodium, and urinary osmolality were measured before and after treatment. Results: Indomethacin treatment caused a significant decrease in urinary ADH excretion (21.8 ± 20.8 vs. 13.8 ± 12.9 pg/ml; p < 0.05), along with a significant reduction in urinary sodium (92.1 ± 36.1 vs. 64.8 ± 35.6; p < 0.05), fractional excretion of sodium (68.5 ± 37.1 vs. 45.6 ± 37.1; p < 0.05), and urinary osmolality (276.2 ± 103.9 vs. 226.4 ± 60.3; p < 0.05). Ibuprofen treatment did not modify urinary ADH excretion and caused a statistically insignificant decrease in urinary sodium and in fractional excretion of sodium. Conclusions: Compared with ibuprofen, indomethacin caused a significant reduction in urinary ADH excretion and a significant decrease in urinary sodium and osmolality.
Anaemia of Cancer: Impact on Patient Fatigue and Long-Term Outcome
Authors: Harper Peter , Littlewood Timothy
Published: October 2005

Anaemia is the most common haematological abnormality encountered by cancer patients. A large European survey of cancer patients (n = 15,367) reported that 67% had anaemia at some point during the survey, and that over 60% of these patients did not receive any treatment for their anaemia. Two other surveys (the FATIGUE surveys) showed that over 75% of cancer patients experienced fatigue at least monthly, with over 30% reporting this symptom on a daily basis. Significantly, patients regarded fatigue as having a greater negative impact on their daily lives than many other cancer- or treatment-related complications, with important emotional and mental consequences including lack of self-motivation, sadness, frustration, and mental exhaustion. Indeed, fatigue was considered so debilitating, 12% of patients felt their quality of life (QoL) was so reduced that they did not wish to continue living. Anaemia is also recognised as an independent predictor of poor prognosis in cancer patients. A systematic review evaluating survival showed a 65% overall increase in the risk of mortality in cancer patients with anaemia. Increasing physicians’ awareness of the importance of effectively treating anaemia in cancer patients therefore has the potential to improve prognosis as well as QoL.
Anaemia Management Strategies: Optimising Treatment Using Epoetin Beta (NeoRecormon®)
Authors: Glaspy John , Beguin Yves
Published: October 2005

Anaemia has a detrimental impact on quality of life and it is important that this condition is recognised and treated in patients with cancer. Epoetin beta is an effective and well-tolerated treatment of anaemia in patients with a wide range of solid and haematological malignancies. A study in patients with lymphoid malignancies confirms that epoetin beta is equally effective at the same overall weekly dose (30,000 IU weekly) when given once-weekly or three-times weekly. This once-weekly regimen has also proved effective in patients with solid tumours. Once-weekly treatment is more convenient for the patient, potentially improving compliance and is associated with reduced hospital administration costs. The majority of patients with cancer will respond to epoetin therapy with an increase in haemoglobin levels. However, it is of value to identify those patients who are likely to respond, so that cost-effectiveness can be improved. Despite much research into potential predictive factors, follow-up studies are required and clinical judgement remains key to managing the anaemia of cancer. In addition, studies suggest that intravenous iron supplementation can improve response to epoetin therapy in patients with functional iron deficiency. Epoetin beta offers an effective, safe and convenient therapy for the management of anaemia in patients with cancer. Ongoing studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.
New Guidelines on Anaemia Management in Patients with Cancer: How Do These Affect Clinical Practice?
Authors: Birgegård Gunnar , Bokemeyer Carsten
Published: October 2005

Anaemia is a condition that frequently occurs in patients with cancer, but a recent survey has cast doubt over whether it is being appropriately treated. These findings are disappointing considering the wealth of data showing the effectiveness of epoetin therapy in patients with cancer. Recently, evidence-based guidelines have been published that aim to provide physicians with the latest information required for optimal management of anaemia in patients with cancer. By increasing physician awareness of the appropriate therapy for anaemia management, more patients may receive the benefits of epoetin therapy.
A Novel Autosomal Recessive Non-Syndromic Deafness Locus, DFNB66, Maps to Chromosome 6p21.2-22.3 in a Large Tunisian Consanguineous Family
Authors: Tlili Abdelaziz , Männikkö Minna , Charfedine Ilhem , Lahmar Imed , Benzina Zeineb , Ben Amor Mohamed , Driss Nabil , Ala-Kokko Leena , Drira Mohamed , Masmoudi Saber , Ayadi Hammadi
Published: October 2005

Hereditary non-syndromic deafness is extremely heterogeneous. Autosomal recessive forms account for approximately 80% of genetic cases. Autosomal recessive non-syndromic sensorineural deafness segregating in a large consanguineous Tunisian family was mapped to chromosome 6p21.2-22.3. A maximum lod score of 5.36 at Θ = 0 was obtained for the polymorphic microsatellite marker IR2/IR4. Haplotype analysis defined a 16.5-Mb critical region between microsatellite markers D6S1602 and D6S1665. The screening of 3 candidate genes, COL11A2, BAK1 and TMHS, did not reveal any disease causing mutation, suggesting that this is a novel deafness locus, which has been named DFNB66. A search in the Human Cochlear EST Library for ESTs located in this critical interval allowed us to identify several candidates. Further investigations on these candidates are needed in order to identify the deafness-causing gene in this Tunisian family.
Impact of a Genetic Polymorphism of the Interleukin-1 Receptor Antagonist on Technique Survival in Peritoneal Dialysis Patients
Authors: Uchiyama Koichi , Naito Katsusuke , Tsuchida Masahiro , Takai Kimio , Okayama Naoko , Fujimura Kozue , Hinoda Yuji
Published: October 2005

Background/Aims: There is a clear association between one allele of the interleukin-1 receptor-antagonist gene (IL-1RN) and inflammatory diseases in which IL-1 is implicated. We evaluated patient survival and technique survival of peritoneal dialysis (PD) patients, while analyzing independent risk factors, in a PD program. We also tested the association between IL-1RN polymorphism, patient survival and technique survival. Methods: We retrospectively evaluated 129 Japanese CAPD patients undergoing initial treatment in eight centers in Japan. Using PCR, IL-1RN genotype and allele frequencies were determined, and clinical and biochemical variables were recorded at the start of PD. The relation of patient survival or technique survival with IL-1RN polymorphism and those variables was analyzed with a multivariate Cox’s proportional-hazard model. Results: The frequencies of IL-1RN*1/IL-1RN*1 and IL-1RN*1/IL-1RN*2 genotypes were 84.5 and 15.5%, respectively. Median patient survival was 37.0 months, and overall patient survival was 92.8 and 87.9% at 2 and 5 years, respectively. Age, cardiovascular disease and serum albumin were found to be independent predictors of patient survival. Median technique survival was 32 months. PD failure occurred in 37 patients, with technique survival rates of 92.0 and 72.7% at 2 and 5 years, respectively. Serum albumin, peritonitis and the presence of the IL-1RN*2 genotype were found to be independent predictors of technique survival. Conclusion: Serum albumin was the strongest predictive factor for mortality and technique failure in PD. Technique failure was also affected by IL-1RN polymorphism in this patient population.
Metabolic Acidosis in Peritoneal Dialysis Patients: The Role of Residual Renal Function
Authors: Tian Xin-kui , Shan Yi-sheng , Zhe Xing-wei , Cheng Li-tao , Wang Tao
Published: October 2005

Background: Metabolic acidosis (MA) is common in chronic renal insufficiency (CRI) patients, and its pattern changes as renal function deteriorates. Although the prevalence of acidosis in peritoneal dialysis has been reported to be rather high, the causes of it have not been well studied. The present study was performed to examine the prevalence of metabolic acidosis in our continuous ambulatory peritoneal dialysis (CAPD) patients and its possible causes. Methods: In this cross-sectional study, we analyzed data from patients who received maintenance CAPD in our hospital and had been on dialysis for at least one month. Patients’ demographic features, medications, and intercurrent medical conditions were recorded. Data including blood biochemistry, dialysis adequacy, and nutrition were collected. A serum bicarbonate concentration of less than 23 mmol/l was defined as having acidosis. The normal value of the serum anion gap (AG) was defined as 12 ± 4 mmol/l. Results: A total of 154 patients (76 males and 78 females) with age of 60.04 ± 13.92 years and the time on dialysis of 16.83 ± 21.59 months were included in this study. Sixty-six patients (43%) had a serum bicarbonate of less than 23 mmol/l, among whom 12 patients (8%) were identified as having MA with increased AG, 54 (35%) were identified as having MA with normal AG. Patients who had better residual renal function (RRF) had a significantly lower serum bicarbonate level despite their higher total KT/Vurea as compared to those with lower RRF. In addition, patients with MA and normal AG had the highest RRF and highest total KT/Vurea. All patients with MA and increased AG had significantly lower values of dietary protein intake (DPI) as compared to their values of normalized protein nitrogen appearance (nPNA), and had higher serum urea and phosphate levels as compared with those patients without MA. Conclusion: Our study suggested that CAPD patients with better RRF were more susceptible to metabolic acidosis, which was characterized by normal anion gap and hyperchloremia. Thus, we speculate that renal loss of bicarbonate may to a large extent be responsible for the occurrence of MA in these patients.