bluuebunny/crossref_metadata_2025 huggingface dataset:
HYDROSTATIC EQUILIBRIUM OF INSULAR, STATIC, SPHERICALLY SYMMETRIC, PERFECT FLUID SOLUTIONS IN GENERAL RELATIVITY
Authors: NEGI P. S.
Published: December 2004

An analysis of insular solutions of Einstein's field equations for static, spherically symmetric, source mass, on the basis of exterior Schwarzschild solution is presented. Following the analysis, we demonstrate that the regular solutions governed by a self-bound (that is, the surface density does not vanish together with pressure) equation of state (EOS) or density variation cannot exist in the state of hydrostatic equilibrium, because the source mass which belongs to them, does not represent the "actual mass" appears in the exterior Schwarzschild solution. The only configuration which could exist in this regard is governed by the homogeneous density distribution (i.e. the interior Schwarzschild solution). Other structures which naturally fulfill the requirement of the source mass, set up by exterior Schwarzschild solution (and, therefore, can exist in hydrostatic equilibrium) are either governed by gravitationally-bound regular solutions (i.e. the surface density also vanishes together with pressure), or self-bound singular solutions (i.e. the pressure and density both become infinity at the centre).
"COMMITTING TO PLACE" AND EVALUATING THE HIGHER PURPOSE: INCREASING ENGAGEMENT IN NATURAL RESOURCE MANAGEMENT THROUGH MUSEUM OUTREACH AND EDUCATIONAL ACTIVITIES
Authors: VANCLAY FRANK , LANE RUTH , WILLS JOANNA , COATES IAN , LUCAS DAMIAN
Published: December 2004

The Australian "Committing to Place" Research Project investigates the potential of outreach activities and educational programmes to increase community commitment to natural resource management. New communication technologies offer tools for enhancing participation — in terms of a deeper commitment from communities and participation of a wider range of groups — through their interactive qualities and capacity to link people in different places. The research project evaluates the piloting, by the National Museum of Australia, of several innovative outreach activities which use information and communication technologies specifically for community capacity building and developing platforms for change. With an understanding of evaluation as research to inform decision-making at all phases of project design, the Research Team is evaluating: (1) the effectiveness of each outreach activity in meeting stakeholder objectives, including community participants; (2) the potential each activity has to increase participation in the activity and other activities associated with cultural heritage or natural resources; and (3) progress towards "the higher purpose", that is, the potential for such activities to affect natural resource management outcomes in the long run. The research project is an Australian Research Council Linkage Grant involving the University of Tasmania, the National Museum of Australia, and the Murray–Darling Basin Commission.
INTEGRATION OF THE SUSTAINABLE DEVELOPMENT EVALUATION PROCESS IN REGIONAL PLANNING: PROMISES AND PROBLEMS IN THE CASE OF FRANCE
Authors: BERTRAND FRANÇOIS , LARRUE CORINNE
Published: December 2004

The paper outlines how the sustainable regional development evaluation process is integrated within the planning and management cycle in the French context. Among the regions that have established reliable evaluation systems, some have tried to incorporate issues relating to sustainable development, thereby complying with European and national demands. But an overview of experiments made in the different French regions shows a wide variety of situations, with no single coordinated procedure allowing comparisons to be drawn. By way of example, the way this integration is implemented in the Nord-Pas-de-Calais region is presented. In this region, political backing, due largely to the presence of green representatives in the regional council, enabled considerable upstream work to be carried out, notably concerning strategic environmental evaluation and policy evaluation with regard to sustainable development. Finally, the paper presents the outcomes of the evaluation process with regard to sustainable regional development: an effect of inter-institutional decompartmentalisation leading to greater transversality have been noticed, as well as a process of an active awareness-raising. But a gap between technical and political levels is still noticeable.
Analysis of hystereses in force length and force calcium relations
Authors: Yaniv Yael , Sivan Raphael , Landesberg Amir
Published: December 2004

Analysis of the hystereses in the force-length relationship at constant Ca2+concentration and in the force-calcium relationship at constant sarcomere length (SL) provides insight into the mechanisms that control cross-bridge (XB) recruitment. The hystereses are related here to two mechanisms that regulate the number of strong XBs: the cooperativity, whereby the number of strong XBs determines calcium affinity, and the mechanical feedback, whereby the shortening velocity determines the duration for which the XBs are in the strong state. The study simulates the phenomena and defines the role of these feedbacks. The model that couples calcium kinetics with XB cycling was built on Simulink software (Matlab). Counterclockwise (CCW) hysteresis, wherein the force response lags behind the SL oscillations, at a constant calcium level, is obtained in the force-length plane when neglecting the mechanical feedback and accounting only for the cooperativity mechanism. Conversely, the force response precedes the SL oscillations, yielding a clockwise (CW) hysteresis when only the mechanical feedback is allowed to exist. In agreement with experimental observations, either CW or CCW hysteresis is obtained when both feedbacks coexist: CCW hystereses are obtained at low frequencies (<3 Hz), and the direction is reversed to CW at higher frequencies (>3 Hz). The cooperativity dominates at low frequencies and allows the muscle to adapt XB recruitment to slow changes in the loading conditions. The changeover frequency from CCW to CW hysteresis defines the velocity limit above which the muscle absorbs rather than generates energy. The hysteresis in the force-calcium relation is conveniently explained by the same cooperativity mechanism. We propose that a single cooperativity mechanism that depends on the number of strong XBs can explain the hystereses in the force-length as well as in the force-calcium relationships.
Comments on “A model for human ventricular tissue”
Authors: Livshitz Leonid , Decker Keith , Faber Gregory , O'Hara Thomas , Silva Jonathan , Rudy Yoram
Published: December 2004

The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue. Comments on “A model for human ventricular tissue” by K. H. W. J. ten Tusscher et al.
Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart
Authors: Chen YingJie , Hou Mingxiao , Li Yunfang , Traverse Jay H. , Zhang Ping , Salvemini Daniela , Fukai Tohru , Bache Robert J.
Published: December 2004

This study examined whether increased superoxide (O2−·) production contributes to coronary endothelial dysfunction and decreased coronary blood flow (CBF) in congestive heart failure (CHF). To test this hypothesis, the effects of the low-molecular-weight SOD mimetic M40401 on CBF and myocardial oxygen consumption (MV̇o2) were examined in dogs during normal conditions and after CHF was produced by 4 wk of rapid ventricular pacing. The development of CHF was associated with decreases of left ventricular (LV) systolic pressure, maximum first derivative of LV pressure, MV̇o2, and CBF at rest and during treadmill exercise as well as endothelial dysfunction with impaired vasodilation in response to intracoronary acetylcholine. M40401 increased CBF (18 ± 5%, P < 0.01) and MV̇o2 (14 ± 6%, P < 0.01) in CHF dogs and almost totally reversed the impaired CBF response to acetylcholine. M40401 had no effect on acetylcholine-induced coronary vasodilation, CBF, or MV̇o2 in normal dogs. Western blot analysis demonstrated that extracellular SOD (EC-SOD) was significantly decreased in CHF hearts, whereas mitochondrial Mn-containing SOD was increased. Cytosolic Cu/Zn-containing SOD was unchanged. Both increased O2−· production and decreased vascular O2−· scavenging ability by EC-SOD could have contributed to endothelial dysfunction in the failing hearts.
Long-Term Challenges in Growth Hormone Treatment
Authors: Cerro A. Leal
Published: December 2004

Growth hormone deficiency (GHD) is defined biochemically as a response to hypoglycaemia with a peak GH concentration of less than 5 µg/l. The ‘GHD syndrome’ is a range of psychological and physical symptoms that are associated with GHD, which include increased central adiposity, decreased bone mineral density, abnormal lipid profiles, decreased cardiovascular performance, reduced lean body mass (LBM), social isolation, depressed mood and increased anxiety. Importantly, the combination of physical and psychological problems can often result in a reduced quality of life. A number of trials have shown that GH replacement therapy can lead to a substantial improvement in GHD associated symptoms. Following up to 12 months of treatment with GH, LBM increased, left ventricular systolic function improved and the mean volume of adipose tissue fell. After only 4 months of treatment, a rise in exercise capacity was recorded, and after 2 years’ treatment, isokinetic and isometric muscle strength had normalized in proximal muscle groups. Feelings of well-being and vitality also improved significantly. However, studies on the effects of treatment on insulin sensitivity in GH-deficient patients have had conflicting results. In this paper, we will discuss the long-term consequences of GHD and the effects of GH replacement therapy.
Cardiovascular Disease and Risk Factors: The Role of Growth Hormone
Authors: Isgaard J.
Published: December 2004

Clinical studies in patients with acromegaly have shown that growth hormone (GH) exerts both short- and long-term effects on the structure and function of the heart. Moreover, chronic growth hormone deficiency (GHD) has been associated with impaired cardiac performance, low heart rate and impaired left ventricular systolic function. Exercise capacity in patients with GHD is significantly reduced and in some severely affected individuals, dilated cardiomyopathy and heart failure has been reported. GHD has also been associated with a number of risk factors for cardiovascular disease. Altered lipoprotein metabolism and elevated fibrinogen and plasminogen activator inhibitor-1 activity are associated with GHD, and the risk of hypertension is increased in GH-deficient men. Subcutaneous and intra-abdominal fat mass have also been found to be abnormally high in these patients. These effects may contribute to an increased risk of death from cardiovascular disease. GH is therefore an important factor in the development and function of the cardiovascular system. In this paper, the effects of GH on the physiological mechanisms of the cardiovascular system are discussed, including the effect of GHD on cardiovascular disease risk. We will also discuss the effects of long-term GH replacement therapy in this patient population.
Eyes Wide Shut? – A Conceptual and Empirical Critique of Methadone Maintenance Treatment
Authors: Fischer Benedikt , Rehm Jürgen , Kim Gregory , Kirst Maritt
Published: December 2004

Background: Methadone maintenance treatment (MMT) has been the ‘gold standard’ pharmacotherapy treatment for illicit opioid dependence for over 30 years. It has been widely evaluated, and is generally claimed to be ‘effective’. Methods: The objective of this paper is to review the rationale of MMT as an intervention for a biomedical disorder with primary social objectives as well as the methodological quality and evidence of MMT outcome research. Data sources included opioid dependence treatment practice, review and outcome research literature (1965–2001) in the form of peer-reviewed articles, books, monographs and reports that are preeminently cited and reviewed international studies on MMT. Results/Data Synthesis: Rigorous and appropriate evaluation (i.e., RCTs, intent-to-treat, patient-centered) methods in MMT evaluations are rare. Evidence of MMT’s effectiveness on primary treatment objectives is mixed and appears to be largely partial and short-term. Positive outcomes may be the result of selection effects of compliant patients and loss in proportion when more rigorous standards of analysis are applied. Conclusions: The quality of existing MMT research, and evidence for its general effectiveness are limited. Key concepts of self-medication and psychiatric comorbidity are largely ignored in MMT treatment and research frameworks, although they may serve to explain MMT’s limited treatment success. Emerging new opioid pharmacotherapies require the fundamental review of the existing MMT paradigm as well as the application of rigorous and appropriate evaluation methods for future treatment.
Long-Term Effects of Family Functioning and Child Characteristics on Problem Drinking in Young Adulthood
Authors: Engels Rutger C.M.E. , Vermulst Ad A. , Dubas Judith S. , Bot Sander M. , Gerris Jan
Published: December 2004

Several studies have shown that disturbances in the parent-child relationship in childhood are related to patterns of alcohol abuse in adolescence and young adulthood. Recently some researchers, however, argue that whether poor parenting is detrimental depends on specific child characteristics. Hence, instead of examining overall effects of parenting, it might be more appropriate to search for specific child-environment effects that lead to problematic drinking patterns. In this paper, we investigate the interplay between child characteristics (lack of self-control and aggression) and parenting on problematic alcohol use in young adulthood. Data were used from a longitudinal study that followed 301 children and their parents for a period of 10 years. Both parents and their children were interviewed on parenting practices and child characteristics when the child was a young adolescent (mean age of 12 years at time 1) and extensive information on problematic alcohol use was gathered when the participants were young adults (mean age was 22 at time 3). Findings showed strong effects of childhood aggression (men only) and poor family functioning on enhanced levels of problem drinking in young adulthood. Further, the combination of high levels of aggression and low levels of family functioning were related to problem drinking in men, whereas the combination of low parental control and low levels of affection expression were related to problem drinking in women.
Percutaneous Vertebroplasty Improves Pain and Physical Functioning in Elderly Osteoporotic Vertebral Compression Fracture Patients
Authors: Liliang Po-Chou , Su Thung-Ming , Liang Cheng-Loong , Chen Han-Jung , Tsai Yu-Duan , Lu Kang
Published: December 2004

Background: Osteoporotic vertebral compression fractures are being recognized increasingly often in the elderly. They frequently cause severe and prolonged back pain and physical decline. Bed rest, narcotic analgesia, and external bracing were the only therapeutic modalities available in the past and had limited success. Objective: The purpose of our study was to determine the efficacy of percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures in the elderly. Methods: Twenty-two vertebroplasties were performed in 16 elderly patients. Pain relief, medication requirements, and physical functioning were evaluated before and 24 h and 6 months after vertebroplasty. Results: There was 81% improvement in pain intensity 24 h after operation, and 94% improvement was noted at the 6-month follow-up checkup. Physical functioning improved 69% 24 h after vertebroplasty and 63% 6 months later. Medication requirements also decreased in 75% of the patients. Conclusion: Percutaneous vertebroplasty for osteoporotic vertebral compression fractures is safe and effective and should not be withheld from the elderly.
Mortality and Blood Pressure in Elderly People with and without Cognitive Impairment
Authors: Cacciatore Francesco , Abete Pasquale , de Santis Domenico , Longobardi Giancarlo , Ferrara Nicola , Rengo Franco
Published: December 2004

Background: Controversial data are available on the association between mortality, blood pressure and cognitive impairment in the elderly. Objective: To verify the role of blood pressure on mortality in an elderly population with and without cognitive impairment. Methods: A cross-sectional survey with a 6-year mortality evaluation was conducted in a region of southern Italy in elderly subjects with and without cognitive impairment. Subjects were divided into 4 groups on the basis of systolic, diastolic, mean and pulse blood pressure values. Results: Mortality shows a linear relationship with pulse blood pressure and a U-curve shape for diastolic blood pressure. This phenomenon was more evident in subjects with cognitive impairment showing the greatest risk of mortality at the lowest and highest levels of diastolic blood pressure. Conclusion: The study shows that mortality increases linearly with increasing blood pressure in the elderly. In contrast, mortality shows a U-shape curve for diastolic blood pressure; cognitively impaired patients with the lowest and highest diastolic blood pressures show the greatest relative risk of mortality.
The Size of the Chi-Square Test for the Hardy-Weinberg Law
Authors: Kang Seung-Ho , Shin Dongwan
Published: December 2004

Many scientific problems can be formulated in terms of a statistical model indexed by parameters, only some of which are of scientific interest and the other parameters, called nuisance parameters, are not of interest in themselves. For testing the Hardy-Weinberg law, a relation among genotype and allele probabilities is of interest and allele probabilities are of no interest and now nuisance parameters. In this paper we investigate how the size (the maximum of the type I error rate over the nuisance parameter space) of the chi-square test for the Hardy-Weinberg law is affected by the nuisance parameters. Whether the size is well controlled or not under the nominal level has been frequently investigated as basic components of statistical tests. The size represents the type I error rate at the worst case. We prove that the size is always greater than the nominal level as the sample size increases. Extensive computations show that the size of the chi-squared test (worst type I error rate over the nuisance parameter space) deviates more upwardly from the nominal level as the sample size gets larger. The value at which the maximum of the type I error rate was found moves closer to the edges of the the nuisance parameter space with increasing sample size. An exact test is recommended as an alternative when the type I error is inflated.
A Recoding Scheme for X-Linked and Pseudoautosomal Loci to Be Used with Computer Programs for Autosomal LOD-Score Analysis
Authors: Strauch Konstantin , Baur Max P. , Wienker Thomas F.
Published: December 2004

We present a recoding scheme that allows for a parametric multipoint X-chromosomal linkage analysis of dichotomous traits in the context of a computer program for autosomes that can use trait models with imprinting. Furthermore, with this scheme, it is possible to perform a joint multipoint analysis of X-linked and pseudoautosomal loci. It is required that (1) the marker genotypes of all female nonfounders are available and that (2) there are no male nonfounders who have daughters in the pedigree. The second requirement does not apply if the trait locus is pseudoautosomal. The X-linked marker loci are recoded by adding a dummy allele to the males’ hemizygous genotypes. For modelling an X-linked trait locus, five different liability classes are defined, in conjunction with a paternal imprinting model for male nonfounders. The formulation aims at the mapping of a diallelic trait locus relative to an arbitrary number of codominant markers with known genetic distances, in cases where a program for a genuine X-chromosomal analysis is not available.
Kenogen in Female Androgenetic Alopecia
Authors: Guarrera M. , Rebora A.
Published: December 2004

Background: Kenogen indicates the physiological interval of the hair cycle in which the hair follicle remains empty after the telogen hair has been extruded and before a new anagen hair emerges. Kenogen frequency and duration are greater in men and women with androgenetic alopecia (AGA). Objective: To study the relationship of kenogen with female AGA. Methods: A woman with AGA, studied 14 years before, was re-examined for 2 years by the phototrichogram technique. Kenogen was identified when telogen lasted 3 months and shedding left the follicle empty. Results: Kenogen lasted 1–5 months, the longest duration affecting cycles of vellus hairs, and involved more hair follicles (16 vs. 8%) than in the first observation. Cycles of vellus hairs increased in number from 4 to 13%, and cycles with a normal succession of phases decreased from 60 to 32%. Conclusions: The number of kenogen phases increased in parallel with vellus hairs and the diminished number of normal hair cycles, features that mark AGA aggravation. Kenogen seems to be related also to the progression of female AGA.
Molecular Identification of Fusarium Species in Onychomycoses
Authors: Ninet Béatrice , Jan Isabelle , Bontems Olympia , Léchenne Barbara , Jousson Olivier , Lew Daniel , Schrenzel Jacques , Panizzon Renato G. , Monod Michel
Published: December 2004

Background:Fusarium species are isolated from about 3% of onychomycoses in the Swiss native population. On the basis of macroscopic characters and microscopic examination of the cultures, identification of Fusarium often remains difficult or uncertain because of variations from one isolate to another and overlapping characteristics between species. Objective: To obtain information about the prevailing species of Fusarium collected from onychomycoses. Methods: An analysis of the Fusarium specimens isolated in the Department of Dermatology at the University Hospital of Lausanne was conducted during a 2-year period (71 isolates). A 311-bp fragment of the gene encoding 28S rRNA was amplified by PCR and sequenced. DNA sequences were compared to those available for reference strains. Results:Fusarium oxysporum was the most frequently isolated species, accounting for 54% of the isolates. F. proliferatum and 4 taxons belonging to the F. solani species complex were identified with an appreciable frequency ranging from 4 to 14%. Conclusion: The Fusarium species identified were the same as those known to cause disseminated fusariosis in immunocompromised patients. The presence of these Fusarium species in onychomycoses warrants that careful attention should be paid to abnormal nails before beginning immunosuppressive treatments in patients.
Androgen Receptor Levels of Oral and Genital Ulcers and Skin Pathergy Test in Patients with Behçet’s Disease
Authors: Alpsoy Erkan , Elpek Gulsum Ozlem , Yilmaz Fikriye , Ciftcioglu Mehmet Akif , Akman Ayse , Uzun Soner , Karakuzu Ali
Published: December 2004

Background: Hormonal factors have long been proposed to play a role in Behçet’s disease (BD). Male sex, systemic onset, HLA-B51 positivity and a younger age of onset in BD are associated with severer disease, and the disease generally runs a milder course in women. Vascular involvement is more common, and the skin pathergy test (SPT) is more strongly positive in men. BD rarely develops before puberty or after the age of 50 years. Clinical manifestations of the disease, with the exception of eye symptoms, tend to improve with time. Therefore, BD may be androgen driven to some degree. Objectives: We aimed to investigate androgen receptor (AR) levels of oral ulcers (OU), genital ulcers (GU) and SPT areas and compared them with those of adjacent normal-appearing skin/mucosa from patients with BD. Methods: Thirty-eight patients with BD (16 female, 22 male; mean ± SD age, 36.45 ± 10.2 years), diagnosed according to the criteria of the International Study Group for Behçet’s Disease, were included in the study with blind histological examination. Biopsies from OU of 10 patients, GU of 11 patients, SPT areas of 17 patients and adjacent (approximately 2 cm distant) normal-appearing skin/mucosa in patients with BD were performed. Nuclear AR levels were studied by an immunohistochemical technique, using monoclonal antibodies. The percentage of positively staining cells was recorded as the AR index (ARI). In addition, the prevalence and the positivity rate of SPT has also been evaluated. Results: ARI values in the lesional and control (non-lesional adjacent) skin/mucosa were found to be 14.5 versus 18% for OU, 28.7 versus 25.5% for GU and 36.3 versus 21.8% (p = 0.068) for SPT areas. The positive SPT areas in male patients showed a higher ARI than those of female patients (43.36 and 23.33%; p = 0.078). The ARI values of SPT areas in male patients but not in female patients were found to be significantly higher as compared with non-lesional skin (21.63%; p = 0.039). The SPT positivity was also more common in male patients compared with female patients (86.4% and 62.5%), although the difference was not significant (p = 0.88). SPT have been found to be more strongly positive among the males (4.63 ± 3.3) compared with female patients (3.18 ± 1.9), and the difference was statistically significant (p = 0.022). Conclusions: Our findings indicate that androgens seem to play a role both in the formation and increased positivity of the SPT areas in male patients with BD.
Updated Swiss Guidelines for the Treatment and Follow-Up of Cutaneous Melanoma
Authors: Dummer R. , Panizzon R. , Bloch P.H. , Burg G.
Published: December 2004

Melanoma is the most common lethal cutaneous neoplasm. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated in 2001. These have been approved by all Swiss medical societies involved in the care of melanoma patients. New data necessitated changes concerning the safety margins (reduction to maximally 2 cm) and modifications of the recommendations of follow-up.
Mild Cutaneous Manifestation in Two Young Women with Extraordinary Hyperandrogenemia
Authors: Chen WenChieh , Chen Guan-Yu , Tsai Shaw-Jenq , Wang Pei-Wen , Sheu Hamm-Ming , Shen Yen-Sheng , Chen Fen-Fen
Published: December 2004

Hyperandrogenism with hyperandrogenemia should be considered in those with severe acne of sudden onset or conspicuous male-pattern baldness with hairline recession, although the majority of female patients with acne or androgenetic alopecia possess no endocrine disorder. Herein we describe on the contrary 2 young women with primary amenorrhea displaying prominent hyperandrogenemia but subtle cutaneous manifestation. The first one presenting vertical alopecia had an elevated level of serum dehydroepiandrosterone sulfate (>800 µg/dl) and was suspected to be a case of late-onset, non-classical adrenal hyperplasia. The second case with mild acne had a soaring serum level of total testosterone >9,000 ng/dl derived from an androgen-secreting adrenal adenoma overexpressing steroidogenic acute regulatory protein, P450 side-chain cleavage enzyme and aromatase. A careful patient history and a complete physical examination are mandatory in each individual female case with acne or alopecia. The possibility of adrenal tumor should be explored in patients with escalated circulating testosterone.
Polymorphous Vascular Patterns in Dermoscopy as a Sign of Malignant Skin Tumors
Authors: Blum Andreas , Metzler Gisela , Bauer Juergen
Published: December 2004

Background: Using dermoscopy (dermatoscopy, epiluminescence microscopy), malignant skin tumors can be detected earlier and unnecessary excisions of benign tumors can be avoided. Objective: Description of the dermoscopic vascular patterns of an amelanotic melanoma and a porocarcinoma. Methods: Dermoscopy of an amelanotic melanoma and a porocarcinoma at 10-fold magnification. Results: On dermoscopy polymorphous vascular patterns with pinpoint and hairpin-like vessels were seen. Conclusion: A reddish tumor without any pigmented network, globules or streaks but with polymorphous vascular patterns must be considered a malignant melanocytic or nonmelanocytic skin tumor.
Pyoderma gangrenosum Preceding the Diagnosis of Systemic Lupus erythematosus
Authors: Waldman Mark A. , Callen Jeffrey P.
Published: December 2004

Patients with systemic lupus erythematosus (SLE) often develop leg ulceration, particularly those with antiphospholipid antibodies or with vasculitis. Pyoderma gangrenosum (PG) is an idiopathic ulcerative neutrophilic dermatosis that is commonly associated with inflammatory bowel disease or seronegative polyarthritis. Although PG-like lesions have been commonly described in patients with the antiphospholipid antibody syndrome, the occurrence of PG as a preceding manifestation of SLE has only rarely been reported. We present a patient who developed PG roughly 8 years prior to developing SLE.
The Ecarin Clotting Time, a Universal Method to Quantify Direct Thrombin Inhibitors
Authors: Nowak Götz
Published: December 2004

The ecarin clotting time (ECT) is a meizothrombin generation test that allows for precise quantification of direct thrombin inhibitors. The ECT has demonstrated its usefulness for more than 10 years in biochemical-pharmacological investigations as well as in clinical research and in the clinical routine. It has proved valuable especially as a drug-monitoring method in r-hirudin therapy. This test has been adjusted to clinical requirements by numerous modifications. Following the description of the biochemical background and the measuring principle of the ECT, this article gives a short survey of several modifications of the ECT for both preclinical and clinical use, e.g., for biochemical investigations, as a point-of-care method and for cardiac surgery. Advantages and disadvantages of these methods are discussed.
Ecarin Chromogenic Assay – A New Method for Quantitative Determination of Direct Thrombin Inhibitors Like Hirudin
Authors: Lange U. , Nowak G. , Bucha E.
Published: December 2004

A new sensitive and precise method for quantitative determination of direct thrombin inhibitors is described, the ecarin chromogenic assay (ECA). Ecarin is used as the specific prothrombin-activating principle. The cleavage of a chromogenic substrate by meizothrombin is inhibited in a concentration-dependent fashion by direct thrombin inhibitors. For the ECA, the linear measuring range is about 0.1–3.0 µg hirudin/ml plasma. Coefficients of variations between 2.3 and 4% over the whole concentration range were achieved. The ECA has proved to be more sensitive than the compared tests (ecarin clotting time and a thrombin-based chromogenic assay); a detection limit of 0.011 µg hirudin/ml and a quantitation limit of 0.032 µg hirudin/ml were calculated. The ECA is independent of the variations of the coagulation variables fibrinogen and prothrombin. Neither heparin nor oral anticoagulants interfere with the ECA.
Low-Molecular-Weight Heparin and Cancer Survival: Review of the Literature and Pooled Analysis of 1,726 Patients Treated for at Least Three Months
Authors: Conti Serenella , Guercini Francesco , Iorio Alfonso
Published: December 2004

Background: Heparin has been the main subject of intensive investigation and clinical use because of its therapeutic anticoagulant properties. It also exhibits many other biological activities, and it was claimed that it shows a beneficial effect on cancer spreading. Searching for papers investigating the effect of low-molecular-weight heparin (LMWH) on cancer mortality we found clinical trials and meta-analyses which showed a reduction in the mortality rate in cancer patients. However, the biological rationale of this effect for a short treatment with LMWH remains unclear. We wanted to check if similar results were achieved in cancer patients treated with LMWH for a longer period of time. Aim: To evaluate the effect on cancer mortality of a 3-month treatment with LMWH by performing a meta-analysis of published studies comparing LMWH and oral anticoagulants (OA) in the prevention of recurrent venous thromboembolism (VTE). Materials and Methods: Computerized searches of Medline and Embase were performed; clinical trials were also located through colleagues and hand scanning of meeting proceedings. Eligibility of the studies and extraction of data were performed by two authors using a standard form. The meta-analysis was performed assuming a fixed-effect model. Results: Eight studies were identified that fulfilled our predefined criteria for a total of 1,726 patients. After a mean of 8.6 months of follow-up, 327 patients had died of cancer, 160 in the LMWH group and 167 in the OA control group (OR 0.95, 95% CI 0.73–1.23; z = 0.42; p = 0.67). Considering cancer mortality in 948 cancer patients the figures were 160/472 in the LMWH group and 167/476 in the OA control group (OR 0.96, 95% CI 0.73–1.25; z = 0.33; p = 0.74). Conclusions: In 1,726 patients randomized to receive a long-term course of at least 3 months of LMWH or OA for the treatment of VTE, no effect on cancer mortality was found.
Lack of Plasminogen Activator Inhibitor-1 Enhances the Preventive Effect of DX-9065a, a Selective Factor Xa Inhibitor, on Venous Thrombus and Acute Pulmonary Embolism in Mice
Authors: Shu En , Matsuno Hiroyuki , Ishisaki Akira , Kitajima Yasuo , Kozawa Osamu
Published: December 2004

We have studied the physiological effects of DX-9065a, a selective factor Xa (FXa) inhibitor, and heparin in experimental venous thrombus and acute pulmonary embolism. Moreover, the effects of these compounds were also evaluated under the condition of plasminogen activator inhibitor-1 (PAI-1) deficiency. A thrombus was induced in the murine femoral vein. The compounds prolonged the time to occlusion in a dose-dependent manner. Pulmonary embolism was induced by continuous induction of venous thrombi in the left jugular vein. The mortality of mice increased time-dependently. Histological evidence of thromboembolism in the lung was obtained in all mice. Treatment with DX-9065a, but not heparin, reduced the mortality at 6 h after initiation of venous thrombi. In separate experiments, pulmonary thromboembolism was induced in PAI-1 knockout mice. The mortality in PAI-1 knockout mice was reduced compared with that of wild-type mice. Moreover, when DX- 9065a was administered to PAI-1 knockout mice with pulmonary thromboembolism, mice survived well without marked bleeding. These findings indicate that the dual inhibition of coagulation FXa and PAI-1 could be beneficial in the treatment of acute pulmonary embolism.
Alterations of the Global Haemostatic Function Test ‘Resonance Thrombography’ in Spontaneously Traumatised Dogs
Authors: Mischke R.
Published: December 2004

Samples taken from 30 dogs with spontaneously acute trauma were investigated with two different resonance thrombographs (instrument 2: 28 dogs), a global method for examination of the haemostatic system. Reaction time of the resonance thrombogram (RTG-r), fibrin generation time (RTG-f), fibrin amplitude (RTG-F) and parameters of platelet function [amplitude of the platelet leg (RTG-P) and descending time of the platelet leg (RTG-p)] were evaluated statistically and compared with a normal control as well as with the results of individual components of the haemostatic system and other screening tests. Comparison of the results of the RTG of dogs suffering from trauma with the normal control revealed differences only for RTG-r, which was longer when measured with instrument 1 and lower RTG-F values measured with both instruments. Depending on the RTG parameter and instrument, only 1–6 samples showed values outside the reference ranges. Only 4 out of 26 cases (resonance thrombograph 2: 2 out of 24 cases) with mild to moderate deficiency in individual coagulation factor activity showed a prolongation of RTG-r which was significantly less sensitive than activated partial thromboplastin time (p < 0.001). Of the 26 samples having mainly mildly to moderately increased fibrin(ogen) degradation product (FDP) levels (median: 39 µg/ml, range: 2–90 µg/ml, reference values: <18 µg/ml) only between 1 and 5 showed abnormalities of the parameters RTG-f and/or RTG-F. The results of this study show in particular the limited sensitivity of the method for detecting individual coagulation factor deficiencies and minimal to moderate increases of FDP concentrations. Remarkable alterations of fibrin generation as measured by the resonance thrombograph are a rare condition in dogs with acute accidental trauma.
Complications of Hydroxyethyl Starch in Acute Ischemic Stroke and Other Brain Injuries
Authors: Wiedermann Christian J.
Published: December 2004

Serious complications of hydroxyethyl starch (HES) administration have been repeatedly demonstrated in clinical trials of acute ischemic stroke and other brain injuries. Such complications have prompted the premature termination of several randomized trials. Coagulopathy and bleeding have been the most frequently documented complications in the brain injury setting and have occurred after exposure to HES solutions of widely varying molecular weight and substitutions. Severe, protracted, refractory pruritus is another HES complication. Claims of safety for HES solutions have often been made on the basis of small trials with inadequate statistical power. Additionally, the safety has been typically assessed in highly selected low-risk patient populations receiving relatively small HES doses, so that the results cannot be generalized to routine clinical practice. The preponderance of available evidence suggests that HES solutions should be avoided in acute ischemic stroke and other brain injuries.
An Investigation into the Effect of the Nitric Oxide Synthase Antagonist L-NAME and Plant Extracts on the Irritability and Barrier Function of the Skin
Authors: Ormerod A.D. , Woo P.N. , Islam J. , Moran J. , Cals-Grierson M.M.
Published: December 2004

Background: Nitric oxide (NO) synthesis is upregulated in dermatitis and may be involved in the modulation of keratinocyte proliferation and formation of the cornified envelope. Objective: To examine the possible effects of modulators of NO production on erythema and transepidermal water loss (TEWL) induced by sodium lauryl sulphate (SLS). Methods: Ten volunteers were patch tested with water and SLS 0.2, 0.5 and 1%. The outcomes of TEWL and erythema were assessed at 1, 6, 25 and 49 h. The effects of the NO inhibitors, L-NAME, extracts of Olea europa and Ginkgo biloba (as 1% gel solutions) and of the NO donor, glyceryl trinitrate (as 2% ointment) were evaluated. Results: L-NAME and the plant extracts reduced TEWL. The TEWL induced by 0.5% SLS was significantly diminished by L-NAME at 1 and 6 h and by ginkgo extract at 6 and 49 h. Erythema was too mild for reflectance measurements to show significant inhibition, but erythema scores tended to be lower at 6 h the application of NO inhibitors. Conclusion: NO inhibitors may protect skin barrier function from the adverse effects of chemical irritants.
A Simplified ELISpot Assay Protocol Used for Detection of Human Interleukin-4, Interleukin-13 and Interferon-γ Production in Response to the Contact Allergen Nickel
Authors: Minang Jacob T. , Ahlborg Niklas , Troye-Blomberg Marita
Published: December 2004

Background: The ELISpot assay is a potential tool for in vitro diagnosis of contact allergy to nickel (Ni2+). A reduction of the assay time and work should further facilitate the development of ELISpot-based clinical and diagnostic applications. Objective: It was the aim of this study to evaluate a simplified ELISpot protocol utilizing plates precoated with capture monoclonal antibody (mAb) and one-step detection by an enzyme-labelled mAb. Methods: The frequency of Ni2+-induced IFN-γ-, IL-4- or IL-13-producing cells in human peripheral blood mononuclear cells from Ni2+-reactive and non-reactive subjects was determined. The simplified ELISpot was performed in parallel with a regular ELISpot assay utilizing overnight adsorption of capture mAb and detection in 2 steps. Results: Ni2+-induced IL-4 and IL-13 production was significantly greater in Ni2+-reactive subjects compared to the controls. The number of antigen-specific, cytokine-producing cells determined by the 2 different ELISpot protocols correlated well. Conclusion: The simplified ELISpot protocol provides a more rapid and easy alternative to the regular ELISpot, with a similar detection sensitivity for antigen-specific T-cell responses.
Heterogeneous Microcirculation in the Rat Small Intestine during Hemorrhagic Shock: Quantification of the Effects of Hypertonic-Hyperoncotic Resuscitation
Authors: Vajda K. , Szabó Andrea , Boros M.
Published: December 2004

Purpose: In the event of a spatial or temporal microvascular perfusion heterogeneity conventional methods are often inadequate to describe the microcirculatory changes. Our aim was to use a new formula to characterize and compare the microcirculatory reactions in the mucosa and longitudinal muscle of the rat small intestine in response to hypertonic/hyperoncotic and normotonic resuscitation strategies. Methods: Intravital videomicroscopy with an orthogonal polarization spectral (OPS) imaging technique was utilized. Microcirculatory variables were recorded during hemorrhagic shock (HS; 50 mm Hg mean arterial pressure for 60 min) and fluid replacement with 0.9% saline or with 7.2% saline containing 10% hydroxyethylstarch 200/0.5 (Osmohes; 4 ml/kg). Due to the temporal perfusion variability, microcirculatory changes were described using the calculation of the average red blood cell velocity (A-RBCV), while the spatial changes were calculated as a function of the size of the perfused capillary network. Results: During HS and the late phase of resuscitation, perfusion was characterized by capillary flow motion (i.e. variability in time) in the villi, and by spatial flow heterogeneity in the longitudinal muscle layer. The approximately 40% decrease in the calculated villus A-RBCV during HS was only partially affected by 0.9% saline, whereas Osmohes completely restored A-RBCV by increasing both the red blood cell velocity and the duration of high-flow periods at the onset of resuscitation in the villi. The approximately 60% reduction in A-RBCV in the muscle layer during HS was not followed by an appreciable recovery in either group, but Osmohes significantly increased A-RBCV in the late resuscitation phase. Conclusions: The hypertonic/hyperoncotic solution induces a considerable microcirculatory improvement in two distinct layers of the small intestine after HS. This positive effect is related to the amelioration of the intestinal microcirculatory heterogeneity.
Beneficial Effect of Hyperbaric Oxygen Therapy on Liver Regeneration after 90% Hepatectomy in Rats
Authors: Nagamine K. , Kubota T. , Togo S. , Nagashima Y. , Mori M. , Shimada H.
Published: December 2004

Background/Aims: Hyperbaric oxygen therapy (HBOT) has been reported to augment oxygen delivery to ischemic tissues and improve the liver dysfunction in clinical cases. HBOT was performed after 90% hepatectomy in rats to determine its effect on the regeneration of remnant liver. Methods: After 90% hepatectomy was performed in 8-week-old male Wistar rats, the animals were subdivided into an HBOT (2 atm abs., 80% O2, 1 h/day, 3 days) group and a non-HBOT group. Members of both groups were sacrificed, usually every 4 h until a maximum of 50 h after hepatectomy, and the liver regeneration rate, the proportion of PCNA-positive cells and the ATP volume in the remnant tissues were examined. Results: In the HBOT group, the liver regeneration rate at 36 h and 50 h after operation and the proportion of PCNA positive cells at 8 h was significantly increased compared with the non-HBOT group. The ATP volume in the remnant livers in the HBOT group was also significantly increased at 12 h. Conclusion: HBOT augmented liver regeneration after hepatectomy by stabilization of energy metabolism induced by oxygen delivery in rats.
Biodegradation of Absorbable Sutures in Body Fluids and pH Buffers
Authors: Freudenberg S. , Rewerk S. , Kaess M. , Weiss Christel , Dorn-Beinecke A. , Post S.
Published: December 2004

Objective: This study measures the influence of body fluids on the loss of tensile strength of absorbable sutures in vitro. Methods: Nine synthetic absorbable sutures were incubated in different gastrointestinal fluids, as well as in blood and three buffers. Stretch tests were performed after days 0, 7, 14, and 21. Results: Tensile strength varied from 18.5 to 32.8 N, and elasticity varied from 9.5 to 51% of the initial length. The influence of pH, blood, and gastric juice was negligible on all sutures except PDS II®. Except for Monocryl®, all sutures, especially Polysorb® and Vicryl®, lost tensile strength much faster in bile, jejunal and pancreatic juices than in the corresponding buffers. Conclusion: The biodegradation of sutures varies greatly in different body fluids independent of differences in pH.