bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and anatomical outcome of anterior and posterior vaginal prolapse repair with prolene mesh
Authors: Milani Rodolfo , Salvatore Stefano , Soligo Marco , Pifarotti Paola , Meschia Michele , Cortese Marina
Published: December 2004

Objective  To evaluate the effects of prolene mesh on urinary, bowel and sexual function in prolapse surgery.

Design  Prospective observational study on consecutive women.

Setting  Two referral uorgynaecological units in Italy.

Population  Women requiring prolapse repair for anterior or posterior vaginal prolapse.

Methods  All women were assessed for urinary, bowel, prolapse symptoms and dyspareunia pre‐ and post‐operatively. Urodynamics was performed in selected cases. Surgery consisted of an anterior or posterior repair plus a prolene mesh. Follow up was after 1, 6 and 12 months. The ANOVA test was used for statistical analysis.

Main outcome measures  Vaginal anatomical restoration, urinary, bowel and sexual function.

Results  We recruited 63 women (mean age 63 years) with a mean follow up of 17 months. Anatomically, the success rate was 94%. Thirty‐two women had an anterior repair. Among this group, the sexual activity rate did not alter but dyspareunia increased by 20%. Urge and stress incontinence did not change post‐operatively but urgency improved in 10% and 13% had vaginal erosion of the mesh. Thirty‐one women had a posterior repair. Among this group, sexual activity decreased by 12% and dyspareunia increased in 63%. Constipation improved in 15% and anal incontinence in 4%, and 6.5% of women had vaginal erosion of the mesh and one required mesh removal for pelvic abscess.

Conclusions  Although this study shows good anatomical results with the use of prolene mesh for prolapse repair, there was a high rate of morbidity. We believe that the use of prolene mesh should be abandoned.
Concentration of cord serum placenta growth factor in normal and diabetic pregnancies
Authors: Loukovaara Mikko , Leinonen Pekka , Teramo Kari , Andersson Sture
Published: December 2004

Objective  To investigate whether maternal diabetes or diabetes‐related complications, such as macrosomia and chronic fetal hypoxia, are associated with altered placenta growth factor (PlGF) levels in cord serum.

Design  Case–control study.

Setting  Helsinki University Central Hospital, Helsinki, Finland.

Population  Sixty‐two normal pregnancies, 67 pregnancies complicated by type 1 diabetes and 28 pregnancies complicated by insulin‐treated gestational diabetes.

Methods  Cord serum PlGF concentration was measured by an enzyme‐linked immunosorbent assay. Amniotic fluid erythropoietin concentration was measured by a chemiluminescent immunologic method. Umbilical artery gas variables were analysed with standard blood gas and pH electrodes.

Main outcome measure  PlGF concentration in cord serum at birth.

Results  Cord serum PlGF concentration was similar in normal pregnancies [13.4 (1.0) ng/L], in pregnancies complicated by type 1 diabetes [15.1 (1.8) ng/L, P= 0.583 vs controls] and in pregnancies complicated by insulin‐treated gestational diabetes [13.6 (0.9) ng/L, P= 0.991 vs controls]. Cord serum PlGF did not correlate with relative birthweight. In diabetic pregnancies, cord serum PlGF correlated negatively with amniotic fluid erythropoietin (r=−0.449, P < 0.0001) and positively with umbilical artery Po2 (r= 0.333, P= 0.001). There was a trend toward lower cord serum PlGF levels in diabetic pregnancies with pre‐eclampsia compared with those without any hypertensive disorders.

Conclusions  Maternal diabetes per se is not associated with altered PlGF levels in cord serum. The correlation between PlGF and indices of fetal hypoxia in diabetic pregnancies may be related to the role of PlGF in potentiating the angiogenic response to vascular endothelial growth factor in ischaemia.
De‐bugging the ‘millipede’ porphyroblast microstructure: a serial thin‐section study and 3‐D computer animation
Authors: JOHNSON S. E. , MOORE R. R.
Published: December 2004

ABSTRACT Seventy‐five spatially orientated, serial thin sections cut from a single rock containing ‘millipede’ porphyroblast microstructure from the Robertson River Metamorphics, Australia, reveal the three‐dimensional (3‐D) geometry of oppositely concave microfolds (OCMs) that define the microstructure. Electronic animations showing progressive serial sections of the 3‐D microstructure are made available via the World Wide Web. The OCM amplitudes decrease regularly from a maximum in near‐central sections to a minimum in near‐marginal sections, whereas the OCM interlimb angles increase regularly from a minimum in near‐central sections to a maximum in near‐marginal sections. These observations illustrate that the OCMs are noncylindrical surfaces with culminations located in near‐central sections. Because the porphyroblast cores appear to have been present before significant development of the syn‐OCM foliation, all of the OCMs were formed by heterogeneous extension around these cores. The overall geometry of the OCMs described here reflects the strain state, and cannot be used to constrain deformation paths.
Corundum–quartz‐bearing assemblage in the Ihouhaouene area (In Ouzzal, Algeria)
Authors: GUIRAUD M. , KIENAST J.‐R. , OUZEGANE K.
Published: December 2004

Granulite facies quartzites from the Ihouhaouene region, in the northern part of In Ouzzal, contain the assemblage corundum+quartz+magnetite together with hercynitic spinel+quartz+magnetite, sillimanite+quartz+magnetite and almandine‐rich garnet+quartz+magnetite. Two types of corundum have been recognized: the first is primary and is found with quartz and magnetite only; the second type is found together with magnetite and chlorite rimming spinel as a fine‐grained corona. The textures show that spinel‐rich magnetite probably exsolved primary corundum, sillimanite, spinel and garnet during the cooling history. The secondary corundum formed later from the spinel already exsolved from magnetite. The secondary corundum is certainly metastable with respect to quartz. This may also apply for the primary corundum. However, given the high‐temperature setting of this rock, it cannot be excluded that the stable contacts observed between primary corundum and quartz indicate equilibrium between the two phases. Taking into account the uncertainties in the thermodynamic data, the stability of this assemblage would imply that this part of In Ouzzal has recorded very high P–T conditions, above 1100°C at 12 kbar.
A review of the In Ouzzal granulitic terrane (Tuareg shield, Algeria): its significance within the Pan‐African Trans‐Saharan belt
Authors: CABY R.
Published: December 2004

The In Ouzzal terrane (IOT) or In Ouzzal granulite unit (IOGU) is an elongated Palaeoproterozoic block within the Neoproterozoic Pan‐African belt of north‐west Africa. The granulites derive from Archaean protoliths that include a large volume of metasediments which were deposited on a 3.2‐Ga gneissic basement. Near‐peak granulite facies conditions between 2.17 and 2 Ga were estimated at P=10 kbar and T rising from 800 to 1000°C. Premetamorphic orthogneisses were intruded at 2.5 Ga, and followed by the emplacement of syn‐ to late‐kinematic charnockites, syenites and carbonatites at around 2 Ga. Cooling of the granulites occurred till 1800 Ma. Shortly after its exhumation coeval with crustal extension and related alkaline magmatism in adjacent areas, the IOT was buried beneath late Palaeoproterozoic and Neoproterozoic cover sequences, and then behaved as a rigid block. Both margins are lithospheric faults, as evidenced by the occurrence of shear‐zone‐related mafic and felsic plutons. Pan‐African tectonothermal events were negligible in the north, but granulites in the south were significantly reworked under lower greenschist facies conditions during the northern motion of the block with respect to both the western and the eastern Pan‐African terranes. The Cambrian molasse, associated with widespread alkaline volcanism and subvolcanic granites, is horizontal in the north. The IOT, which was part of a larger continental mass including its counterpart in northern Mali, is interpreted as an exotic terrane which may have docked during Pan‐African plate convergence and lateral collision. The unchanged pediplain since c. 1.7 Ga in the north suggests that the IOT is underlain by thick Palaeoproterozoic lithospheric mantle, whereas its southern part is probably allochthonous and overlies Pan‐African structural units.
Metasomatic effects related to channelled fluid streaming through deep crust: fenites and associated carbonatites (In Ouzzal Proterozoic granulites, Hoggar, Algeria)
Authors: FOURCADE S. , KIENAST J.‐R. , OUZEGANE K.
Published: December 2004

The In Ouzzal granulitic unit (IOGU) consists predominantly of felsic orthogneisses most of which correspond to granitoids emplaced during the Archaean, plus metasediments, including olivine‐spinel marbles, of late Archaean age. All units were metamorphosed at granulite facies during the Eburnean (2 Ga). The stable isotope signature of the marbles (δ13C=–0.8 to –4.2‰/PDB; δ18O = 7.9 to 18.9‰/SMOW) does not record a massive streaming of C‐bearing fluids during metamorphism. Most of the isotopic variation in the marbles is explained in terms of pregranulitic features. Metasomatic transformation of granulites into layered potassic syenitic rocks and emplacement of carbonate veins and breccias occurred during retrogressive granulite facies conditions. The chemistry of these rocks is comparable with that of fenites and carbonatites with high contents of (L)REEs, Th, U, F, C, Ba and Sr but, with respect to these elements, a relative depletion in Nb, Ta, Hf, Zr and Ti. The isotopic compositions of Nd (ɛNd(T)=–6.3 to –9.9), of Sr (87Sr/86Sr(T)= 0.7093–0.7104), and the O isotopic composition of metasomatic clinopyroxene (δ18O = 6.9 to 8‰), all indicate that the fluid had a strong crustal imprint. On the basis of the C isotope ratios (δ13C =–3.5 to –9.7‰), the fluid responsible for the crystallization of carbonates and metasomatic alteration is thought to be derived from the mantle, presumably through degassing of mantle‐derived magmas at depth. Intense interaction with the crust during the upward flow of the fluid may explain its chemical and isotopic signatures. The zones of metasomatic alteration in the In Ouzzal granulites may be the deep‐seated equivalents of the zones of channelled circulation of carbonated fluids described at shallower levels in the crust.
Paragonite–hornblende assemblages and their petrological significance: an example from the Austroalpine Schneeberg Complex, Southern Tyrol, Italy
Authors: KONZETT J. , HOINKES G.
Published: December 2004

ABSTRACT Paragonite‐bearing amphibolites occur interbedded with a garbenschist‐micaschist sequence in the Austroalpine Schneeberg Complex, southern Tyrol. The mineral assemblage mainly comprises paragonite + Mg‐hornblende/tschermakite + quartz + plagioclase + biotite + ankerite + Ti‐phase + garnet ± muscovite. Equilibrium P–T conditions for this assemblage are 550–600°C and 8–10 kbar estimated from garnet–amphibole–plagioclase–ilmenite–rutile and Si contents of phengitic muscovites. In the vicinity of amphibole, paragonite is replaced by symplectitic chlorite + plagioclase + margarite +± biotite assemblages. Muscovite in the vicinity of amphibole reacts to form plagioclase + biotite + margarite symplectites. The reaction of white mica + hornblende is the result of decompression during uplift of the Schneeberg Complex. The breakdown of paragonite + hornblende is a water‐consuming reaction and therefore it is controlled by the availability of fluid on the retrogressive P–T path. Paragonite + hornblende is a high‐temperature equivalent of the common blueschist‐assemblage paragonite + glaucophane in Ca‐bearing systems and represents restricted P–T conditions just below omphacite stability in a mafic bulk system. While paragonite + glaucophane breakdown to chlorite + albite marks the blueschist/greenschist transition, the paragonite + hornblende breakdown observed in Schneeberg Complex rocks is indicative of a transition from epidote‐amphibolite facies to greenschist facies conditions at a flatter P–T gradient of the metamorphic path compared to subduction‐zone environments. Ar/Ar dating of paragonite yields an age of 84.5 ± 1 Ma, corroborating an Eoalpine high‐pressure metamorphic event within the Austroalpine unit west of the Tauern Window. Eclogites that occur in the Ötztal Crystalline Basement south of the Schneeberg Complex are thought to be associated with this Eoalpine metamorphic event.
The Importance of Integrated Goal Setting: The Application of Cost-of-Capital Concepts to Private Firms
Authors: Adams A. Frank , Manners George E. , Astrachan Joseph H. , Mazzola Pietro
Published: December 2004

In this article, we examine financial return, answer the question of how one knows when the return is adequate, and explore the relationship of short- and long-term returns as they relate to business health.
Selection Testing via the Internet: Practical Considerations and Exploratory Empirical Findings*
Authors: POTOSKY DENISE , BOBKO PHILIP
Published: December 2004

Despite a growing body of applied research on using the Internet for some human resource management practices, few studies have provided equivalence information or practical lessons concerning selection testing via the Internet. We identify several issues associated with measurement and validity, the role of several individual characteristics, respondents' reactions and behaviors, and other considerations concerning Internet test administration. We also report results from an exploratory study of the correlation between paper‐and‐pencil and Internet‐administered cognitively oriented selection tests (including timed and untimed, proctored tests). Our empirical results suggest modest degrees of cross‐mode equivalence for an untimed situational judgment test (r= .84) and for a timed cognitive ability test (r= .60). Further, some types of items (math, verbal, spatial) in the timed cognitive ability test seem to play a differential role in the reduced cross‐mode equivalence. New issues regarding the perception of, and reaction to, items presented via the Internet are presented, and a variety of practical issues are derived and discussed.
A METHOD FOR ENVIRONMENTAL SUSTAINABILITY ASSESSMENT: THE CASE OF THE POLISH REGIONS
Authors: GOŃCZ ELŻBIETA , KISTOWSKI MARIUSZ
Published: December 2004

Integrated planning for regional development is relatively new in Poland, following the reform of the territorial administration in 1999. The strategic plans now produced by the regional parliaments are crucial research documents, particularly for their orientation to environmental and regional sustainable development objectives. This research developed and tested an assessment framework of issues for each regional plan. This was framed first in terms of internal regional objectives, and second in terms of their role in national level plans and policies. Such vertical integration of planning systems is a major challenge for European multi-level systems of governance. The assessment framework uses a system of indicators and indices, comparing regional versus national conditions and trends, based on a simple rational/maximal model. The methodology was designed to be transferable to other territorial levels, and may become a practical tool for evaluation of structural funding in similar regions across the EU. The methodology will benefit from further enhancements, in particular for the indicator set used for the 2000–2010 regional sustainable development model. However, at this stage in the development of Polish strategic planning, it aims to provide a starting point for sustainability impact assessment of all major policy proposals, in the spirit of the Göteborg principles for European sustainable development.
A HOLARCHICAL MODEL FOR REGIONAL SUSTAINABILITY ASSESSMENT
Authors: JILIBERTO HERRERA RODRIGO
Published: December 2004

This paper is an attempt to develop a holarchical paradigm for regional sustainability assessment based on a critic of the epistemology of sustainability, seen as between two polar opposites that make up a unified system.

On the one hand we find what can be described as a representationalist view, for which sustainability is the result of juxtaposing certain economic, social and environmental aspects of reality. However, complexity and uncertainty are the most relevant epistemological results of trying to define sustainability as an "objective" entity derived from an analytical perspective.

On the other hand, complexity and uncertainty lead to the conclusion that sustainability cannot be expressed and, therefore, the problem of what to do does not depend so much on the description of the object we want to act on, but on how we decide what to do. This is the procedural epistemology of sustainability.

The methodological and epistemological proposal that has guided the development of the Sustainable Development Strategy for the Region of Murcia, for instance, is equidistant from these two options. It is based on the belief that it is necessary and possible to constitute sustainability as an analytically coherent (i.e. non-arbitrary) object of knowledge, which is at the same time autonomous from the analytical–fragmentary descriptions that comprise standard scientific knowledge. In the centre of this epistemology is a systemic understanding of "reality" that tries to grasp the hierarchical inter-existence of the outer world, and focuses primarily on contingent management from a dynamic viewpoint rather than that of certainty.

This epistemological dual perspective has many implications for evaluation practice, both in the framing of technical analysis, and in the management of social participation.
Accelerated LV remodeling after myocardial infarction in TIMP-1-deficient mice: effects of exogenous MMP inhibition
Authors: Ikonomidis John S. , Hendrick Jennifer W. , Parkhurst Andrea M. , Herron Amanda R. , Escobar Patricia G. , Dowdy Kathryn B. , Stroud Robert E. , Hapke Elizabeth , Zile Michael R. , Spinale Francis G.
Published: December 2004

Alterations in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been implicated in adverse left ventricular (LV) remodeling after myocardial infarction (MI). However, the direct mechanistic role of TIMPs in the post-MI remodeling process has not been completely established. The goal of this project was to define the effects of altering endogenous MMP inhibitory control through combined genetic and pharmacological approaches on post-MI remodeling in mice. This study examined the effects of MMP inhibition (MMPi) with PD-166793 (30 mg·kg−1·day−1) on LV geometry and function (conductance volumetry) after MI in wild-type (WT) mice and mice deficient in the TIMP-1 gene [TIMP-1 knockout (TIMP1-KO)]. At 3 days after MI (coronary ligation), mice were randomized into four groups: WT-MI/MMPi ( n = 10), TIMP1-KO-MI/MMPi ( n = 10), WT-MI ( n = 22), and TIMP1-KO-MI ( n = 23). LV end-diastolic volume (EDV) and ejection fraction were determined 14 days after MI. Age-matched WT ( n = 20) and TIMP1-KO ( n = 28) mice served as reference controls. LVEDV was similar under control conditions in WT and TIMP1-KO mice (36 ± 2 and 40 ± 2 μl, respectively) but was greater in TIMP1-KO-MI than in WT-MI mice (48 ± 2 vs. 61 ± 5 μl, P < 0.05). LVEDV was reduced from MI-only values in WT-MI/MMPi and TIMP1-KO-MI/MMPi mice (42 ± 2 and 36 ± 2 μl, respectively, P < 0.05) but was reduced to the greatest degree in TIMP1-KO mice ( P < 0.05). LV ejection fraction was reduced in both groups after MI and increased in TIMP1-KO-MI/MMPi, but not in WT-MI/MMPi, mice. These unique results demonstrated that myocardial TIMP-1 plays a regulatory role in post-MI remodeling and that the accelerated myocardial remodeling induced by TIMP-1 gene deletion can be pharmacologically “rescued” by MMP inhibition. These results define the importance of local endogenous control of MMP activity with respect to regulating LV structure and function after MI.
Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles
Authors: Schäfer S. C. , Wallerath T. , Closs E. I. , Schmidt C. , Schwarz P. M. , Förstermann U. , Lehr H.-A.
Published: December 2004

Long-term treatment with glucocorticoids is associated with mild to moderate hypertension. We reported previously that downregulation of endothelial NO synthase (eNOS) expression and activity is likely to contribute to this increase in blood pressure. In the present study, we tested the effects of dexamethasone on the vasodilation of microvascular arterioles using implanted dorsal skin-fold chambers in anesthetized C57BL/6J mice. Experiments were performed on control mice or on mice treated with dexamethasone (0.1–3 mg/kg of body wt). Endothelium-dependent vasodilation in response to ACh (0.1–10 μM) was reduced by dexamethasone in a dose-dependent fashion. Comparable inhibition was seen in tissues superfused with 30 μM NG-nitro-l-arginine methyl ester. In contrast, endothelium-independent vasodilation in response to S-nitroso- N-acetyl-d,l-penicillamine (10 μM) was not influenced by either dexamethasone or NG-nitro-l-arginine methyl ester. Levels of eNOS mRNA in murine hearts and NO2−/NO3−in serum were suppressed by dexamethasone (down to 63 and 50% of control values, respectively, at 3 mg/kg of body wt) along with a reduction in eNOS protein to 85.6%. Dexamethasone also concentration dependently reduced the expression of the cationic amino acid transporter-1 in murine hearts and cultured endothelial cells. The suppression by dexamethasone of the ACh-induced vasodilation could be partially reversed by dietary l-arginine (50 mg/kg of body wt) and by dietary vitamin C (10 g/kg of diet). We conclude that suppression by dexamethasone of the endothelium-mediated microvascular vasodilation involves several mechanisms including 1) downregulation of eNOS, 2) downregulation of cationic amino acid transporter-1, and 3) generation of reactive oxygen species. The demonstration that l-arginine and vitamin C can partially offset the effects of dexamethasone on microvascular arterioles suggests the potential clinical usefulness of these agents for the reduction of glucocorticoid-induced hypertension.
Angiotensin-induced defects in renal oxygenation: role of oxidative stress
Authors: Welch William J. , Blau Jonathan , Xie Hui , Chabrashvili Tina , Wilcox Christopher S.
Published: December 2004

We tested the hypothesis that superoxide anion (O2−·) generated in the kidney by prolonged angiotensin II (ANG II) reduces renal cortical Po2and the use of O2for tubular sodium transport (TNa:QO2). Groups ( n = 8–11) of rats received angiotensin II (ANG II, 200 ng·kg−1·min−1sc) or vehicle for 2 wk with concurrent infusions of a permeant nitroxide SOD mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, 200 nmol·kg−1·min−1) or vehicle. Rats were studied under anesthesia with measurements of renal oxygen usage and Po2in the cortex and tubules with a glass electrode. Compared with vehicle, ANG II increased mean arterial pressure (107 ± 4 vs. 146 ± 6 mmHg; P < 0.001), renal vascular resistance (42 ± 3 vs. 65 ± 7 mmHg·ml−1·min−1·100 g−1; P < 0.001), renal cortical NADPH oxidase activity (2.3 ± 0.2 vs. 3.6 ± 0.4 nmol O2−··min−1·mg−1protein; P < 0.05), mRNA and protein expression for p22phox(2.1- and 1.8-fold respectively; P < 0.05) and reduced the mRNA for extracellular (EC)-SOD (−1.8 fold; P < 0.05). ANG II reduced the Po2in the proximal tubule (39 ± 1 vs. 34 ± 2 mmHg; P < 0.05) and throughout the cortex and reduced the TNa:QO2(17 ± 1 vs. 9 ± 2 μmol/μmol; P < 0.001). Tempol blunted or prevented all these effects of ANG II. The effects of prolonged ANG II to cause hypertension, renal vasoconstriction, renal cortical hypoxia, and reduced efficiency of O2usage for Na+transport, activation of NADPH oxidase, increased expression of p22phox, and reduced expression of EC-SOD can be ascribed to O2−· generation because they are prevented by an SOD mimetic.
Role of ATP-sensitive K+ channels in electrophysiological alterations during myocardial ischemia: a study using Kir6.2-null mice
Authors: Saito Tomoaki , Sato Toshiaki , Miki Takashi , Seino Susumu , Nakaya Haruaki
Published: December 2004

The role of cardiac ATP-sensitive K+ (KATP) channels in ischemia-induced electrophysiological alterations has not been thoroughly established. Using mice with homozygous knockout (KO) of Kir6.2 (a pore-forming subunit of cardiac KATP channel) gene, we investigated the potential contribution of KATP channels to electrophysiological alterations and extracellular K+ accumulation during myocardial ischemia. Coronary-perfused mouse left ventricular muscles were stimulated at 5 Hz and subjected to no-flow ischemia. Transmembrane potential and extracellular K+ concentration ([K+]o) were measured by using conventional and K+-selective microelectrodes, respectively. In wild-type (WT) hearts, action potential duration (APD) at 90% repolarization (APD90) was significantly decreased by 70.1 ± 5.2% after 10 min of ischemia ( n = 6, P < 0.05). Such ischemia-induced shortening of APD90 did not occur in Kir6.2-deficient (Kir6.2 KO) hearts. Resting membrane potential in WT and Kir6.2 KO hearts similarly decreased by 16.8 ± 5.6 ( n = 7, P < 0.05) and 15.0 ± 1.7 ( n = 6, P < 0.05) mV, respectively. The [K+]o in WT hearts increased within the first 5 min of ischemia by 6.9 ± 2.5 mM ( n = 6, P < 0.05) and then reached a plateau. However, the extracellular K+ accumulation similarly occurred in Kir6.2 KO hearts and the degree of [K+]o increase was comparable to that in WT hearts (by 7.0 ± 1.7 mM, n = 6, P < 0.05). In Kir6.2 KO hearts, time-dependent slowing of conduction was more pronounced compared with WT hearts. In conclusion, the present study using Kir6.2 KO hearts provides evidence that the activation of KATP channels contributes to the shortening of APD, whereas it is not the primary cause of extracellular K+ accumulation during early myocardial ischemia.
A Case of Mistaken Identity
Authors: Stahl Andreas
Published: December 2004

The heart is a unique organ that can use several fuels for energy production. During development, the heart undergoes changes in fuel supply, and it must be able to respond to these changes. We have examined changes in the expression of several genes that regulate fuel transport and metabolism in rat hearts during early development. At birth, there was increased expression of fatty acid transporters and enzymes of fatty acid metabolism that allow fatty acids to become the major source of energy for cardiac muscle during the first 2 wk of life. At the same time, expression of genes that control glucose transport and oxidation was downregulated. After 2 wk, expression of genes for glucose uptake and oxidation was increased, and expression of genes for fatty acid uptake and utilization was decreased. Expression of carnitine palmitoyltransferase I (CPT I) isoforms during development was different from published data obtained from rabbit hearts. CPT Iα and Iβ isoforms were both highly expressed in hearts before birth, and both increased further at birth. Only after the second week did CPT Iα expression decrease appreciably below the level of CPT Iβ expression. These results represent another example of different expression patterns of CPT I isoforms among various mammalian species. In rats, changes in gene expression followed nutrient availability during development and may render cardiac fatty acid oxidation less sensitive to factors that influence malonyl-CoA content (e.g., fluctuations in glucose concentration) and thereby favor fatty acid oxidation as an energy source for cardiomyocytes in early development.
Advances in Growth Hormone Therapy: A New Registry Tool
Authors: Pugeat M.
Published: December 2004

Growth hormone (GH) deficiency is a rare condition, and physicians may lack clinical experience of its treatment. Despite evidence for the efficacy and tolerability of GH therapy, a substantial proportion of patients remain untreated. Registries and other large-scale databases are an important tool for expanding the evidence base for GH treatment. Since the mid-1980s, registries have provided data on important aspects of the safety and efficacy of GH treatment. Registries have also allowed pooling of data from patients with rare conditions that could otherwise not be recruited in sufficient numbers for clinical trials. Importantly for patients and their relatives, use of registry data has allowed the development of prediction models that indicate the likely outcomes of treatment. MEGHA (Metabolic Endocrinology and Growth Hormone Assessment) is a recently developed, observational database with a number of features not found in existing registries, including its use as a day-to-day clinical management tool, the ability to create individual sub-studies, direct comparison of personal data against the full database, and a particular focus on the transition from childhood to adulthood. This creative registry is a promising instrument for further research into GH-related disorders that will improve GH therapy and thus provide benefits for patients.
Bridging Regional and Global Perspectives
Authors: Heufelder A.
Published: December 2004

In recent years, medical practice has evolved towards greater reliance on evidence-based medicine. Societies and reimbursement agencies often publish recommendations for treatment based on literature review and trial data. Despite this, growth hormone (GH) replacement therapy in adults varies substantially from region to region. The reasons for this include differing beliefs in quality of life benefits, the cost-effectiveness of GH and the role of GH in reducing cardiovascular mortality. Reimbursement varies from almost complete take-up in Sweden and Germany, to strict guidelines in the UK, while in some countries GH is not reimbursable for adults with GH deficiency, leaving patients open to the short- and long-term consequences of the condition. Clearly, there is a need for further evidence regarding the overall value of GH replacement. Randomized, controlled trials are the foundation of evidence-based medicine, but long-term treatment is difficult to assess in such trials. Thus, there is an important role for large-scale registries in gathering evidence. For example, the MEGHA (Metabolic Endocrinology and Growth Hormone Assessment) database provides participants with a sub- studies function, allowing them to create and design collective, observational studies to investigate areas of GH medicine that are of particular interest or concern to them and their patients.
Stepping into Adulthood: The Transition Period
Authors: Shalet S.
Published: December 2004

The period of growth from late puberty to full adult maturation, termed the transition period, is important for tissue maturation. Peak bone mass, muscle mass and strength are usually attained in this period. However, it is common clinical practice in children with growth hormone deficiency (GHD) to discontinue growth hormone (GH) treatment in adolescence after attainment of final height. Therefore, patients with childhood-onset GHD that continues into adulthood and who do not receive treatment as adults may experience more severe consequences than patients who acquire GHD as an adult. Recent studies indicate that bone and muscle maturation are attenuated if GH treatment is discontinued at final height. Furthermore, these patients will also develop cardiovascular risk factors that are normally associated with GHD in adults. Much debate surrounds when retesting for GHD should be carried out and when GH treatment should be restarted in adolescents; many of these patients will not have severe GHD according to the criteria set for adults. The transition period is an appropriate time to modify GH doses. Finally, registries exist that have recorded clinical treatment experiences for children and adults. Tools that collect and analyse data provide an important opportunity to investigate issues related to transition.
Significance of Comorbidity for the Long-Term Course of Opiate Dependence
Authors: Verthein Uwe , Degkwitz Peter , Haasen Christian , Krausz Michael
Published: December 2004

Objective: Studies on drug dependence show a high prevalence of comorbidity with additional mental disorders. Comorbidity patients also show more poly-substance use and other psychosocial problems. This study analyzed the importance of comorbidity for the long-term course of opiate dependence. Method: 350 opiate-dependent patients were examined at yearly follow-ups over 4 years using the EuropASI for the assessment of drug-related problems and the CIDI for diagnostic of psychiatric disorders. 196 patients were reached at final follow up (56%). Results: Of the patients reached at final follow-up, 30% had severe, 29% mild and 41% no clinically relevant disorders at baseline. However, the linear relationship at baseline – the more severe the disorder, the greater the impairment through drug-related problems – was not present at final follow-up. The results show that lifetime diagnosis of mental disorder had no prognostic relevance for the long-term course of drug dependency. Conclusion: The assumption that opiate users with an additional mental disorder are more vulnerable in their course of addiction could not be confirmed.
Addictive Behaviour of Adolescents in Secondary Schools in Hungary
Authors: Nyári Tibor A. , Herédi Katalin , Parker Louise
Published: December 2004

Objective: To investigate drug use among secondary schoolchildren aged 14–18 years in the city of Szeged in Hungary in order to observe and describe drug use, smoking and alcohol intake and to find risk factors for these behaviours. Methods: The questionnaire was concerned with recreational drug use, smoking and drinking habits as well as family structure and life-style based upon the European School Project on Alcohol and Other Drugs questionnaire. Statistical methods used were the χ2 test and multiple logistic regression analysis. The standard errors were estimated using the Huber-White procedure. Results: Overall 20% of schoolchildren reported experience of drug usage. Boys were significantly more likely to report drug use than girls (χ2 = 4.65; p = 0.031). Cannabis was the most commonly reported drug used (96%). The proportion of drug users was significantly higher among those who had smoked (13%) or were current smokers (65%) compared to those who never smoked (1%; χ2 = 164.7; p < 0.001). Moreover, the risk of drug use was significantly higher in those children who reported a drug user in the family (OR 9.3; 95% CI 4.3–19.9; p < 0.001). Conclusions: Our findings support the hypothesis that strategies for the prevention of drug use should consider the association between drug and tobacco use.
Dual-Task-Related Gait Changes in
Authors: Beauchet Olivier , Dubost Véronique , Gonthier Régis , Kressig Reto W.
Published: December 2004

Background: Changes in gait patterns due to a simultaneously performed cognitive task have been reported previously and associated with an increased falling risk among older adults. Little is known whether the type of cognitive task performed while walking is important concerning possible gait interference in older fall-prone individuals. Objective: To quantify and compare the effects of two different cognitive tasks on gait in transitionally frail older adults. Measurements: Gait was tested in 30 transitionally frail older adults (mean age 82.6 ± 7.1 years, 90% female) while either walking alone, performing a simple arithmetic task, or performing a task of verbal fluency. Walking time in seconds, number of steps, frequency of lateral line stepping-over, and stops were recorded. Health status was assessed using standard instruments of geriatric assessment. The classification of Speechley and Tinetti was used to define the participants’ degree of frailty. Results: Walking time and number of steps increased significantly under both dual-task conditions compared to walking alone (p < 0.001) without reaching a significant difference between the two dual-task conditions (respectively, p = 0.131 and p = 0.407), whereas lateral gait instability (frequency of lateral line stepping-over) increased significantly in association with counting backward (p = 0.006) but not with the verbal fluency task (p = 1). Conclusion: Among the studied sample of transitional older adults, a walking- associated arithmetic task significantly interfered with lateral gait stability, whereas no lateral gait deviations were seen in association with a verbal fluency task. We, therefore, suggest that the choice of the attention-splitting task in dual-task gait assessment among older adults must be made carefully.
A 4-Year Follow-Up of Very Old Patients Presenting with Frontal-Subcortical Dysfunction Compared with Alzheimer’s Disease Patients
Authors: Pfitzenmeyer Pierre , Mourey France , Manckoundia Patrick , d’Athis Philippe
Published: December 2004

Background: Frontal-subcortical clinical syndrome (FSCS) is frequently described in elderly patients and consists of specific alterations in cognition and motor functions. This clinical picture may be associated with a high level of dependence and a high mortality risk. Objective: We report the risks of institutionalization and death during a follow-up of 4 years in patients showing FSCS. Methods: The study was initiated in 1998 to compare FSCS patients showing postural and gait abnormalities with Alzheimer’s disease (AD) patients. Follow-up was conducted by means of telephone interviews with the patient’s general practitioner over a 4-year period (1998–2002). Results: Both institutionalization and mortality rates were significantly higher (p < 0.05) in the FSCS group compared to the AD group. Conclusions: The high risk of disability and death in FSCS patients suggests that they might require specific care programs that include stimulation in daily living activities in order to reduce the risk of institutionalization and to improve quality of life.
Attitudes to Restraint for the Prevention of Falls in Hospital
Authors: Vassallo Michael , Wilkinson Charlie , Stockdale Rachel , Malik Naveed , Baker Roger , Allen Stephen
Published: December 2004

Introduction: Fall prevention measures in hospital are often considered to be restraint and unsuitable for clinical practice. The aim of the study was to explore attitudes to restraint and what are acceptable fall prevention measures in hospital. Methods: A structured questionnaire was completed by 200 subjects (100 patients/relatives and 100 care professionals) in a British hospital. Results: Ninety-nine percent agreed that fall prevention was important. There was 84.5% agreement that restraint is justified to prevent harm and 81.5% disagreement that restraint should never be used if the patient is at risk of falling. Disagreement was stronger among patients/relatives (91 vs. 72%; p = 0.001). Seventy seven percent disagreed that restraint is not acceptable even if discussed with patients and relatives. Significant differences in agreement were identified between patients/relatives and care professionals for the following statements: ‘restraint should always be an option in patients if the patient is at risk of falling’ (82 vs. 45%; p < 0.0001), ‘restraining methods are acceptable at the discretion of care professionals’ (91 vs. 43%; p < 0.0001), ‘restraint is an infringement of personal freedom’ (35 vs. 66%; p < 0.0001) and ‘restraint is necessary if it frees staff to do more clinical work’ (51 vs. 10%; p < 0.0001). A wide range of acceptability was identified for various measures of restraint: observation beds (95%), bed/chair alarms (80%), bed rails (77%), identification bracelets (95%) and risk labels at the head of the bed (75.5%). Direct binding (5.5%) or tranquilliser use (9%) was considered highly unacceptable. Conclusions: When there is a lack of evidence of effectiveness, fall prevention guidelines are formulated on the basis of expert opinion influenced by ethical considerations, cultural attitudes and society’s values. Such information is important to formulate informed fall prevention policies.
Effect of Population Stratification on Case-Control Association Studies
Authors: Gorroochurn Prakash , Hodge Susan E. , Heiman Gary , Greenberg David A.
Published: December 2004

There has been considerable debate in the literature concerning bias in case-control association mapping studies due to population stratification. In this paper, we perform a theoretical analysis of the effects of population stratification by measuring the inflation in the test’s type I error (or false-positive rate). Using a model of stratified sampling, we derive an exact expression for the type I error as a function of population parameters and sample size. We give necessary and sufficient conditions for the bias to vanish when there is no statistical association between disease and marker genotype in each of the subpopulations making up the total population. We also investigate the variation of bias with increasing subpopulations and show, both theoretically and by using simulations, that the bias can sometimes be quite substantial even with a very large number of subpopulations. In a companion simulation-based paper (Heiman et al., Part I, this issue), we have focused on the CRR (confounding risk ratio) and its relationship to the type I error in the case of two subpopulations, and have also quantified the magnitude of the type I error that can occur with relatively low CRR values.
The Conundrum of Skin Pores in Dermocosmetology
Authors: Uhoda Emmanuelle , Piérard-Franchimont Claudine , Petit Ludivine , Piérard Gérald E.
Published: December 2004

‘Skin pore’ is a term used by lay people and in the field of cosmetology. It remains misleading when it is not clearly defined. Indeed, lay people use it with at least 3 different meanings. Basically, invisible pores represent the openings of the sweat gland apparatus. By contrast, the visible pores represent enlarged empty funnel-shaped or cylindrical horny impacted openings of pilosebaceous follicles. This review describes some of the current objective methods used to describe skin pores.
Ten Years of Skin Malignancies in a Single General Practice
Authors: Shapley M.
Published: December 2004

Background: Generalists within the UK have for many years been performing minor surgical procedures. Little has been published concerning this activity. Objectives: To determine the management of skin malignancy in a UK general practice in order to allow comparison of activity with other practices and disciplines and to identify areas for research. Methods: Retrospective cohort study in an urban 4-partner general practice of 10,000 patients. Total ascertainment of all diagnosed skin malignancies over 10 years achieved by undertaking computerised searches. Results: 136 skin malignancies were identified in 101 patients. The recurrence rates for basal cell carcinomas managed in primary care were comparable to rates published for secondary care. A quarter of patients developed a metachronous skin malignancy or a recurrence. Conclusion: Almost half of all skin malignancies were wholly managed within primary care. There appeared to be no consistent pattern of management. There is a need for research and consensus on optimal care.
Relevance of Thyroiditis and of Other Autoimmune Diseases in Children with Vitiligo
Authors: Iacovelli Paolo , Sinagra Jolinda L.M. , Vidolin Andrea Paro , Marenda Samantha , Capitanio Bruno , Leone Giovanni , Picardo Mauro
Published: December 2004

Background: Studies that clearly define the possible association of childhood vitiligo with autoimmune and/or endocrine diseases are lacking. Objective: To examine the presence of autoimmune disorders, in particular of thyroid disease, in paediatric patients with vitiligo and investigate the utility of such screening in these patients. Methods: One hundred and twenty-one paediatric patients (40 males, 81 females) with vitiligo were grouped in segmental and non-segmental vitiligo. All patients were screened for thyroid disease. Results: 13 out of 121 patients had different degrees of thyroid parameter alterations. These patients were all affected by the non-segmental type while none of those with the segmental form presented thyroid alterations. Conclusion: In paediatric patients with non-segmental vitiligo, a significant incidence of thyroid dysfunction was found. Since vitiligo usually appears before the development of the thyroid disease, it may be useful to screen thyroid autoantibodies in all paediatric patients with non-segmental vitiligo who present symptoms related to thyroid disease.
Elastosis perforans serpiginosa Associated with Pseudo-Pseudoxanthoma elasticum during Treatment of Wilson’s Disease with Penicillamine
Authors: Bécuwe Cécile , Dalle Stéphane , Ronger-Savlé Sandra , Skowron François , Balme Brigitte , Kanitakis Jean , Thomas Luc
Published: December 2004

Background: Elastosis perforans serpiginosa (EPS) is a reactive perforating dermatosis characterized by the elimination of abnormal elastic fibers from the upper dermis through the epidermis. In a few cases, it occurs as a side effect of treatment by D-penicillamine (DPA). The first case of EPS induced by DPA was described in 1972 in a patient treated for Wilson’s disease. Subsequently, cutaneous changes resembling pseudoxanthoma elasticum (PXE) were observed in patients treated with DPA and were reported as pseudo-PXE. Case Report: We report herein the clinical, pathological and ultrastructural study of 2 new cases of DPA-induced EPS and pseudo-PXE. These patients had been treated for Wilson’s disease since 14 and 16 years, respectively. Characteristic abnormal elastic fibers were found on histopathological examination of both EPS and pseudo-PXE skin and confirmed by an ultrastructural study. There was no ABCC6 mutation. Discussion: Penicillamine is able to induce widespread, cutaneous and systemic, elastic fiber damage. Our patients present typical features of DPA-induced elastosis, presenting as EPS and pseudo-PXE. ABCC6 mutation is associated with PXE and, as expected, it was absent in our cases of pseudo-PXE. This elastopathy has been related to morphologic changes in elastic fibers secondary to prolonged therapy in most cases. DPA may interfere with elastin cross-linking through inhibition of the enzyme lysyl oxidase, or by formation of complexes with the cross-linked precursors, impairing a normal maturation of elastic fibers. However, no fatal complication of DPA-induced elastopathy has been reported so far. An improvement of the cutaneous lesions is expected after the drug discontinuation.
Normal Functional Protein S Activity Does Not Exclude Protein S Deficiency
Authors: Rodger Marc A. , Carrier Marc , Gervais Muriel , Rock Gail
Published: December 2004

Protein S (PS) deficiency appears to increase the risk of venous thrombosis. PS deficiency is classified into three phenotypes using antigenic levels and functional activity. By definition, all three phenotypes of PS deficiency should result in low activated protein C cofactor activity. We compared the results of functional PS activity testing to free antigenic PS testing in order to determine if a normal functional PS activity assay result could eliminate the need for free antigenic PS testing. The sensitivity of the functional assay is 45.5% (95% confidence interval, CI, 36–55%), specificity 95.3% (95% CI 93–97%), negative predictive value 88.6% (95% CI 86–91%) with a positive predictive value of 68.5% (95% CI 57–79%). In conclusion, a normal functional PS activity result does not exclude free antigenic PS deficiency. Functional PS activity testing should not be used as a screening test to eliminate free antigenic PS testing for the laboratory diagnosis of PS deficiency.