bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro Studies of the Penetration of Adhesive Resins into Artificial Caries–Like Lesions
Authors: Robinson C. , Brookes S.J. , Kirkham J. , Wood S.R. , Shore R.C.
Published: April 2003

Instead of removing the porous carious tissue at a relatively late stage in the disease process, attempts have been made to ‘fill’ the microporosities of lesions at a much earlier stage of lesion development. This would not only reduce the porosity and therefore access of acid and egress of dissolved material, but also afford some mechanical support to the tissue and perhaps inhibit further attack. Successful infiltration of materials into lesions has been demonstrated previously using resorcinol–formaldehyde which, however, was clinically unacceptable. The advent of dental adhesives with potentially suitable properties has prompted a re–examination of this concept. Artificial lesions of enamel were generated in extracted human teeth using acidified gels. A range of currently available adhesive materials was then used to infiltrate the porosities. The extent of occlusion of the lesion porosities was determined both qualitatively using light microscopy and quantitatively using a chloronaphthalene imbibition technique. The effect of such treatment upon subsequent exposure to acid gels was also investigated. Results showed that up to 60% of the lesion pore volume had been occluded following infiltration with some of the materials and that this treatment was capable of reducing further acid demineralization. The development of such treatment strategies could offer potential noninvasive means of treating early enamel lesions.
Dental Amalgam Fillings and the Amount of Organic Mercury in Human Saliva
Authors: Leistevuo J. , Leistevuo T. , Helenius H. , Pyy L. , Österblad M. , Huovinen P. , Tenovuo J.
Published: April 2003

We studied differences in the amounts of organic and inorganic mercury in saliva samples between amalgam and nonamalgam human study groups. The amount of organic and inorganic mercury in whole saliva was measured in 187 adult study subjects. The mercury contents were determined by cold–vapor atomic absorption spectrometry. The amount of organic and inorganic mercury in paraffin–stimulated saliva was significantly higher (p<0.001) in subjects with dental amalgam fillings (n = 88) compared to the nonamalgam study groups (n = 43 and n = 56): loge (organic mercury) was linearly related to loge (inorganic mercury, r2 = 0.52). Spearman correlation coefficients of inorganic and organic mercury concentrations with the number of amalgam–filled tooth surfaces were 0.46 and 0.27, respectively. Our results are compatible with the hypothesis that amalgam fillings may be a continuous source of organic mercury, which is more toxic than inorganic mercury, and almost completely absorbed by the human intestine.
Effect of Time on the Remineralisation of Enamel by Synthetic Saliva after Citric Acid Erosion
Authors: Eisenburger M. , Addy M. , Hughes J.A. , Shellis R.P.
Published: April 2003

The aim of this in vitro study was to determine the influence of remineralisation time on rehardening of surface–softened enamel after citric acid erosion. Seven groups of 13 samples of human enamel were eroded in 0.3% citric acid at pH 3.2 for 2 h followed by profilometric measurements. Individual groups of specimens were placed in artificial saliva for 1, 2, 4, 6, 9 or 24 h. A control group was placed in isotonic saline for 24 h. After new profilometric measurements samples were ultrasonicated stepwise up to 480 s with profilometric measurements performed at 5, 30, 120, 240 and 480 s to measure the depth of surface softening. The control group had a softened surface layer of mean thickness 2.9 µm. Mineral deposition was seen at all remineralisation times by scanning electron microscopy. Exposure to artificial saliva for 1, 2 or 4 h produced a partial rehardening of the softened enamel; the additional surface losses produced by ultrasonication were lower and time delayed compared to the control group. Specimens remineralised for 6, 9 and 24 h showed little evidence of surface loss after ultrasonication. The data suggest that a complete rehardening of the softened enamel in vitro is reached after a remineralisation time of 6 h. These data are of clinical relevance to tooth wear. However, there is a need for studies in situ of enamel demineralisation and remineralisation.
An in–vitro Evaluation of Kodak Insight and Ektaspeed Plus Film with a CMOS Detector for Natural Proximal Caries: ROC Analysis
Authors: Nair M.K. , Nair U.P.
Published: April 2003

This study compared the diagnostic efficacy of Kodak Ektaspeed Plus film, Kodak Insight film, a newly introduced E/F–speed film, and Schick CMOS–APS digital sensor, with respect to caries detection in 92 proximal surfaces of extracted unrestored teeth, 51 of which were carious. Ground truth was evaluated histologically and the lesions classified as enamel or dentinal. Eight observers read the radiographs using a five–point confidence rating scale to record their diagnoses. Analyses using receiver operating characteristic curves revealed the areas under each curve that indicated the diagnostic accuracy (Ektaspeed Plus – 0.760, Insight – 0.778 and CMOS–APS sensor – 0.732). ANOVA revealed significant differences with respect to caries depth (p<0.031) and observers (p<0.0001). Weighted kappa analyses indicated moderate to substantial inter– and intra–observer agreement (0.42 and 0.66, respectively). The results suggest that none of the imaging modalities evaluated in this study differed in their diagnostic capabilities with respect to proximal decay detection and that the Insight film which was used with 20% less radiation exposure than Ektaspeed Plus film was as good as the other two sensors for this purpose.
Total Fluoride Intake and Urinary Excretion in German Children Aged 3–6 Years
Authors: Haftenberger M. , Viergutz G. , Neumeister V. , Hetzer G.
Published: April 2003

There have only been few investigations comparing total fluoride intake and the fluoride proportion excreted in urine in pre–school children. In addition, the results of available studies are conflicting. Total fluoride intake was assessed in 11 healthy children aged 3–6 years on 2 consecutive days and urinary fluoride excretion was determined. The duplicate–diet approach was used for the assessment of fluoride intake from solid and liquid foods. Fluoride intake from toothbrushing was calculated as the difference between the amount of fluoride in the paste put on the toothbrush and the drinking water (fluoride concentration 0.25 mg/l) used for rinsing vs. the fluoride amounts recovered in the toothpaste spat out and in the rinsing water. Use of fluoridated domestic salt and/or fluoride tablets was recorded. The children’s intake of fluoride from food averaged 202.5±116.2 µg F/day. They swallowed an average amount of 273.9±175.6 µg F/day when brushing their teeth. Daily fluoride ingestion from all sources totalled 930.7±391.5 µg or 53.0±21.4 µg/kg body weight. On average 51.5% of the fluoride ingested was excreted in urine. The wide interindividual variation makes it necessary to evaluate the urinary excretion rate for fluoride in larger study populations with varied fluoride exposure.
Pathophysiology of Acute Ischemic Stroke: New Concepts in Cerebral Embolism
Authors: Futrell Nancy
Published: April 2003

Cerebral embolism was once thought to be the etiology of only a small percentage of ischemic strokes. In earlier classification schemes stroke was generally referred to as (1) ‘embolic’ (definite only if a source of embolism was proven, suspected if cerebral infarcts were bilateral), (2) ‘hemodynamic’ (if there was a tight carotid stenosis thought to produce stroke by decreased flow past the stenosis or if there was decreased cardiac output or decreased blood pressure), (3) ‘lacunar’ (implying ‘hypertensive small-vessel disease’ if the stroke was small and deep, even though the patient may not have a history of hypertension) and (4) ‘thrombotic’ (if none of the other 3 ‘mechanisms’ could be demonstrated), which was thought to be the major mechanism for stroke.
Acute Stroke Therapy in Europe Today
Authors: Hennerici M.G.
Published: April 2003

Until a few years ago, and still today, early stroke management has not been considered to be of major importance. Although it is one of the leading causes of death and permanent disability, absorbing a considerable proportion of health care budgets, and different from myocardial infarction which is the other highest-ranking disease in mortality/morbidity statistics in the industrialized countries, stroke has not been considered an emergency, and both general and special treatments for the acute stroke patient have been denied despite evidence to the contrary [1, 2].
Controlling Acute Elevation of Plasma Fibrinogen with Ancrod
Authors: Cole C.Wm.
Published: April 2003

Elevated plasma fibrinogen is an independent risk factor for generalized atherosclerosis. Markers of elevated fibrinogen include cigarette smoking, diabetes, hypertension and a sedentary life-style; all are associated with vascular occlusive disease. A variety of molecular mechanisms have been proposed by which fibrinogen could directly influence the vessel wall [1]. In addition, fibrinogen degradation products stimulate macrophages to produce a variety of factors including interleukin 6, an important mediator of inflammation. For this reason, atherosclerosis could be described as a low-grade, generalized inflammatory condition of the arterial wall. As illustrated in figure 1, the exact role of fibrinogen in these processes is complex and multifocal. This discussion will focus on the management of acute elevations of fibrinogen using ancrod, a thrombin-like enzyme, that triggers a cascade of normal reactions. When these are carefully controlled, fibrinogen can be safely depleted to achieve clinical benefit.
Therapeutic Inhibition of Platelet Function in Stroke
Authors: Harker Laurence A.
Published: April 2003

Platelet-dependent thrombotic- and thromboembolic-occlusive events are the usual cause of ischemic strokes. Antiplatelet strategies target one of the three platelet recruitment pathways (thromboxane A2, adenosine diphosphate, or thrombin) or the common cohesion pathway involving integrin αIIbβ3 fibrinogen receptors. Aspirin selectively and irreversibly interrupts TxA2 and decreases events by 20–25%. Clopidogrel selectively and irreversibly inactivates platelet-ADP receptors and reduces events by 30–35%. Additive effects are produced by combining aspirin and clopidogrel. Integrin αIIbβ3 fibrinogen receptor antagonists, such as abciximab, produce dose-dependent inhibition of platelet recruitment and thrombo-occlusive events, regardless of the agonist(s) initiating platelet activation, but correspondingly impair platelet hemostatic function. Because chronic antiplatelet therapy has the potential for producing abnormal bleeding it is important for current clinical trials to evaluate the benefit risk relationship.
Biology of Arterial Atheroma
Authors: Willeit Johann , Kiechl Stefan
Published: April 2003

Endothelial dysfunction and changes in arterial wall morphology including thickening of the tunica intima, excess synthesis of collagenous matrix (fibroblastic intimal thickening) and permanent or dynamic deposition of lipids (fatty streaks) already occur in childhood or adolescence. Definite atherosclerotic plaques in the carotid arteries usually do not manifest themselves before menopause in women or age 40 in men. Obviously, cumulative (long-term) and excessive exposure of the vessel wall to risk factors is required to overcome highly effective defense mechanisms which have not yet been fully investigated. Initiation and early progression of atherosclerosis rely on conventional vascular risk factors such as hyperlipidemia, hypertension, smoking, severe alcohol consumption and chronic infections. Plaque extension is effectively compensated by a focal widening of the vessel, thereby preventing the development of lumen obstruction (vascular remodeling). For stenosis to emerge conventional plaques must convert to complicated plaques characterized by plaque rupture and consecutive atherothrombosis. This process usually starts with small- to medium-sized plaques. Potential determinants of plaque rupture are the composition of the lesion (large lipid-rich core), damage of the fibrous cap (destabilization by chronic inflammation) and hemodynamic stress. According to pathological observations, fissuring of atherosclerotic lesions is a frequent event, while the formation of overlying large thrombi (with progression of stenosis or vessel occlusion) is definitely rare. This conjecture emphasizes the significance of local and systemic thrombus-promoting factors. Actually, the risk profile of advanced atherogenesis in the Bruneck Study was primarily composed of markers of enhanced prothrombotic capacity, attenuated fibrinolysis and clinical conditions known to interfere with coagulation. Almost all subjects with ≧3 procoagulant risk conditions developed carotid stenosis or showed progression of preexisting stenosis during a 5-year period. Increasing insights into the complex biology of arterial atheroma and awareness of the etiologic peculiarities of advanced complicated plaques may serve as a basis for identifying high-risk subjects and for novel vascular prevention strategies with focus on plaque stabilization and antithrombotic/anticoagulant measures.
Glycine Antagonist (GV150526) in Acute Stroke: A Multicentre, Double-Blind Placebo-Controlled Phase II Trial
Authors: Lees K.R. , Lavelle J.F. , Cunha L. , Diener H.C. , Sanders E.A.C.M. , Tack P. , Wester P.
Published: April 2003

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores ≤5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of ≧95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.
Bootstrap Statistics of ECASS II Data: Just Another post hoc Analysis of a Negative Stroke Trial?
Authors: Stingele R. , Bluhmki E. , Hacke W.
Published: April 2003

The results of the Second European-Australasian Acute Stroke Study (ECASS II) were negative with respect to the primary endpoint. This post hoc analysis of ECASS II data was designed to make the least number of a priori assumptions. This is accomplished by a bootstrap-based hypothesis test on a non-parametric test statistic. No assumptions are made on shape or variance of population distributions and the method does not suffer from the disadvantages of dichotomization. By reducing the number of a priori assumptions, the possibilities to modify the test result by adjusting the test procedure are minimized. Results: If rt-PA does not improve the outcome (null hypothesis), the probability of observing a difference of modified ranking scale equal or larger than the one observed in ECASS II is 0.047. We therefore rejected the null hypothesis.
Differences between Anterior and Posterior Circulation Stroke in TOAST
Authors: Libman R.B. , Kwiatkowski T.G. , Hansen M.D. , Clarke W.R. , Woolson R.F. , Adams H.P.
Published: April 2003

Background and Purpose: Clinicians have tended to view anterior circulation (AC) and posterior circulation (PC) strokes as separate entities, with different underlying pathogenesis, natural histories, and potential responsiveness to interventions such as anticoagulation. We sought to explore differences between AC and PC stroke in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). Methods: For patients enrolled in TOAST, prospective clinical information was collected including outcome at 3 months. Data on vascular distribution were obtained from the clinical impression of the investigators. Group comparisons for categorical data were performed using Fisher’s exact test. Independent sample t tests and analysis of covariance were used for all continuous data. Results: The analysis included 1,039 patients with AC stroke and 180 patients with PC stroke. There were fewer women in the PC than in the AC groups, but otherwise there were no differences in demographics, risk factors or stroke subtypes between the two groups. Headache (AC 8.7%, PC 15%, p = 0.013) and vomiting (AC 3.5%, PC 17.8%, p < 0.001) were more common among PC patients. Mean baseline National Institutes of Health Stroke Scale (NIHSS) score was lower (less severe) among PC (6.1) than AC patients (9.5; p < 0.001). On univariate analysis, favorable outcome at 3 months was more common for PC patients in both the placebo group (PC 82%, AC 71%, p = 0.04) and heparinoid group (PC 87%, AC 73%, p = 0.005). However, multivariate analysis, controlling for gender, history of previous stroke and baseline NIHSS score, showed no difference in outcome between PC and AC stroke. For favorable outcome, there was no interaction between vascular distribution and treatment category, suggesting that the effect of heparinoid did not differ between PC and AC strokes. Conclusion: Patients with PC stroke seem to have a better long-term outcome than do AC patients, but this difference is no longer apparent when controlling for important prognostic variables. PC patients did not show any particular benefit from anticoagulation, and the efficacy of heparinoid did not vary between AC and PC stroke. While AC and PC patients do differ in some respects, it may be inappropriate to single out PC patients for anticoagulant treatment.
Antiepileptic Treatment in Patients with Early Postischemic Stroke Seizures: A Retrospective Study
Authors: Gilad Ronit , Lampl Yair , Eschel Yehiel , Sadeh Menachem
Published: April 2003

Early seizures caused by stroke are a common cause of epilepsy in adults. The protocol for treatment in such a case is not clear. Patients were studied retrospectively after early poststroke seizures. Two groups of patients were compared: one treated group included 35 patients who continued therapy for 2 years; the second group of 23 patients were untreated following a first attack, receiving anticonvulsive therapy only after a second seizure. The data of 61 patients (35 treated and 26 untreated) were analyzed. In the treated group, 24 patients were on treatment with carbamazepine, 9 with valproic acid and 2 with phenytoin. Seizure-free rate after 2 years was 85% in group I and 61% in group II (p = 0.042). Comparing the seizure rate and the event-free period (number/follow-up at risk) during the 2 years of no anticonvulsive therapy, both groups experienced about the same seizure rate (4.8 vs. 6.2%, p = 0.605) and similar seizure-free curve survival analysis (p = 0.85). We conclude that treatment of seizures immediately after the first attack after cerebral infarctions decreases the risk of recurrent seizure during the first 2 years of antiepileptic treatment. This subgroup of patients receiving antiepileptic medication immediately after the first poststroke seizure continues to be at the same rate of risk after treatment was stopped as the untreated group during the first 2 years. Antiepileptic therapy is an option in the medical management of poststroke seizure patients, but has no influence on the development of recurrent seizures after discontinuing medication.
Fatigue after Stroke: A Major but Neglected Issue
Authors: Staub Fabienne , Bogousslavsky Julien
Published: April 2003

Subjective fatigue, defined as a feeling of early exhaustion developing during mental activity, with weariness, lack of energy and aversion to effort, remains virtually unstudied in patients with stroke, bur recent surveys suggest that it is a major, commonly overlooked, stroke sequela. While the few existing series did not show significant correlations between fatigue and stroke severity, lesion location, cognitive and neurological impairment and depression, recent neurobehavioral studies have highlighted an association between fatigue and brainstem and thalamic lesions. This suggests that fatigue may be linked to the interruption of neural networks involved in tonic attention, such as the reticular activating system. In fact, several subtypes of fatigue may develop after stroke, in connection with cognitive sequelae, neurological impairment, psychological factors and sleep disorders. A challenge is to identify and delineate these different subtypes and to distinguish them from mood disorders, which frequently coexist. We emphasize the concept of ‘primary’ poststroke fatigue, which may develop in the absence of depression or a significant cognitive sequela, and which may be linked to attentional deficits resulting from specific damage to the reticular formation and related structures involved in the subcortical attentional network. In the patients with excellent neurological and neuropsychological recovery, poststroke fatigue may be the only persisting sequela, which may severely limit their return to previous activities. The recognition of poststroke fatigue may be critical during recovery and rehabilitation after stroke.
Potential Triggering Factors of Intracerebral Hemorrhage
Authors: Passero Stefano , Ciacci Giuseppe , Reale Fabio
Published: April 2003

The distributions of intracerebral hemorrhage (ICH) according to place of onset, degree of physical activity at onset and potential triggering factors were analyzed in 848 patients with ICH. Patients were grouped according to the presumed cause of ICH: hypertensive ICH, secondary ICH and ICH of undetermined origin. The influence of demographic and temporal factors on the relative frequency of events was also assessed. In 30% of the cases, ICH occurred during inactivity or sedentary activity, in 50% during light exertion and in 20% during moderate/vigorous exertion. During inactivity or sedentary activity, hypertensive ICH was significantly less frequent than secondary ICH (OR 0.32; 95% CI 0.21–0.47) and undetermined ICH (OR 0.36; 95% CI 0.23–0.55), whereas during moderate or vigorous exertion hypertensive ICH was more frequent than secondary (OR 1.88; 95% CI 1.16–3.05) and undetermined ICH (OR 2.29; 95% CI 1.31–4.00) Potential triggering factors were observed in 27% of patients and were significantly more frequent in patients with hypertensive ICH than in patients with secondary ICH (OR 2.90; 95% CI 1.85–4.54) or undetermined ICH (OR 2.44; 95% CI 1.54–3.87). Our findings suggest that many potential external triggers that act mainly by raising blood pressure may interact, and their concurrence may favor cerebral hemorrhage, particularly in hypertensive patients. In many cases, these circumstances of increased risk may be mitigated by preventive measures.
Stroke in Saudi Arabia
Authors: Al Rajeh Saad , Awada Adnan
Published: April 2003

In this review, the authors summarize 10 years of work on stroke in Saudi Arabia that has led to more than 25 publications. The incidence and prevalence of strokes were low when compared to those reported from Western countries, but this was mainly due to the younger age of the population. The overall distribution of stroke types was not different from that reported in other communities, with the exception of the low incidence of subarachnoid hemorrhage. However, the relatively high frequency of strokes in the young and strokes related to small artery disease, i.e. lacunar infarcts and cerebral hemorrhage, and the high prevalence of diabetes mellitus as a risk factor were quite distinctive. On the other hand, extracranial large artery disease was quite rare. Undetected and untreated hypertension and a low frequency of cigarette smoking in the stroke-prone age group could be one explanation of these findings.
Unusually Prolonged Progressing Stroke: An Expanding Anterior Cerebral Artery Infarction
Authors: Ay Hakan , Uluç Kayıhan , Arsava Ethem M. , Saatçi Işıl , Sarıbaş Okay
Published: April 2003

Progressive clinical deterioration over a period of weeks coupled with MRI evidence of infarction growth is quite uncommon. In this report, we describe a patient with an occluded left anterior cerebral artery (ACA) at the origin of the A2 segment. His symptoms attributable to a posteriorly located small infarction within the ACA territory slowly progressed during the following 8 weeks. A follow-up MRI revealed that the infarction had expanded to involve the whole region of the left ACA. Occasional patients like ours indicate that stroke is a dynamic disorder with an extremely variable clinical course and state of tissue injury.
Atherothrombosis as a Systemic Disease
Authors: Drouet Ludovic
Published: April 2003

Atherothrombosis is a generalized disease process that affects large- and medium-diameter arteries throughout the arterial tree. The trigger of the ischaemic clinical events is the complication of a disrupted atherosclerotic plaque by the formation of a platelet-rich thrombus. These thrombotic events are not always clinically manifest; in most cases, the thrombotic reaction remains parietal but contributes to plaque growth by infiltration of the thrombus by smooth muscle cells. In addition, the evolution of the thrombotic reaction destroys the microvasculature of the downstream tissue by subclinical platelet thrombi. Less often, the resulting thrombus leads to partial or total occlusion of the affected artery with subsequent ischaemic clinical manifestations such as ischaemic stroke, unstable angina and Q-wave or non-Q-wave myocardial infarction. The proportion of ischaemic arterial events that is due to atherothrombosis varies according to the vascular bed in which the event occurs, from a near-total dependency for the lower limbs (intermittent claudication) to less than 50% for cerebrovascular events (ischaemic stroke). Occurrence of an arterial ischaemic event due to atherothrombosis implies that other arterial territories may already be affected by a similar pathological process, even if still clinically silent. Treatment of atherothrombotic patients should include the management of cardiovascular risk factors (which aims at the prevention of incidence, evolution and instability of the plaques) and antiplatelet treatment for the prevention of thrombotic complications. Secondary prevention of an ischaemic event in the index territory will provide primary prevention for other arterial territories that are still clinically silent. The aims of antiplatelet therapy are first to prevent the occurrence of acute ischaemic events through inhibition of platelet thrombus formation and second to protect distal tissues through inhibition of microembolization. Due to the systemic nature of the disease, antiplatelet therapy that has shown a proven consistent benefit across all arterial beds is mandatory for optimal prevention of ischaemic events in atherothrombotic patients.
The Origin, Formation and Developmental Significance of the Epicardium: A Review
Authors: Männer J. , Pérez-Pomares J.M. , Macías D. , Muñoz-Chápuli R.
Published: April 2003

Questions on the embryonic origin and developmental significance of the epicardium did not receive much recognition for more than a century. It was generally thought that the epicardium was derived from the outermost layer of the primitive myocardium of the early embryonic heart tube. During the past few years, however, there has been an increasing interest in the development of the epicardium. This was caused by a series of new embryological data. The first data showed that the epicardium did not derive from the primitive myocardium but from a primarily extracardiac primordium, called the proepicardial serosa. Subsequent data then suggested that the proepicardial serosa and the newly formed epicardium provided nearly all cellular elements of the subepicardial and intermyocardial connective tissue, and of the coronary vasculature. Recent data even suggest important modulatory roles of the epicardium and of other proepicardium-derived cells in the differentiation of the embryonic myocardium and cardiac conduction system. The present paper reviews our current knowledge on the origin and embryonic development of the epicardium.
Localization of Cells of the Prospective Neural Plate, Heart and Somites within the Primitive Streak and Epiblast of Avian Embryos at Intermediate Primitive-Streak Stages
Authors: Lopez-Sanchez Carmen , Garcia-Martinez Virginio , Schoenwolf Gary C.
Published: April 2003

By constructing avian transplantation chimeras using fluorescently-labeled grafts and antibodies specific for grafted cells, we have generated a prospective fate map of the primitive streak and epiblast of the avian blastoderm at intermediate primitive-streak stages (stages 3a/3b). This high-resolution map confirms our previous study on the origin of the cardiovascular system from the primitive streak at these stages and provides new information on the epiblast origin of the neural plate, heart and somites. In addition, the origin of the rostral endoderm is now documented in more detail. The map shows that the prospective neural plate arises from the epiblast in close association with the rostral end of the primitive streak and lies within an area extending 250 µm rostral to the streak, 250 µm lateral to the streak and 125 µm caudal to the rostral border of the streak. The future floor plate of the neural tube arises within the midline just rostral to the streak, confirming our earlier study, but unlike at the late-primitive streak stages when both Hensen’s node and the midline area rostral to Hensen’s node contribute to the floor plate, only the area rostral to the primitive streak contributes to the floor plate at intermediate primitive-streak stages. Instead of contributing to the floor plate of the neural tube, the rostral end of the primitive streak at intermediate primitive-streak stages forms the notochord as well as the rostromedial endoderm, which lies beneath the prechordal plate mesoderm and extends caudolaterally on each side toward the cardiogenic areas. The epiblast lateral to the primitive streak and caudal to the neural plate contributes to the heart and it does so in rostrocaudal sequence (i.e., rostral grafts contribute to rostral levels of the straight heart tube, whereas progressively more caudal grafts contribute to progressively more caudal levels of the straight heart tube), and individual epiblast grafts contribute cells to both the myocardium and endocardium. The prospective somites (i.e., paraxial mesoderm) lie within the epiblast just lateral to the prospective heart mesoderm. Comparing this map with that constructed at late primitive-streak stages reveals that by the late primitive-streak stages, prospective heart mesoderm has moved from the epiblast through the primitive streak and into the mesodermal mantle, and that some of the prospective somitic mesoderm has entered the primitive streak and is undergoing ingression.
Severe Personality Changes after Unilateral Left Paramedian Thalamic Infarct
Authors: Fukutake Toshio , Akada Koichi , Ito Shoichi , Okuda Tomoko , Ueki Yoshihiro
Published: April 2003

Personality changes are not uncommon after paramedian thalamic infarction, but usually bilateral or relatively large lesions, often complicated by other neurological or neuropsychological deficits, are present. ‘Pure’ cases of unilateral lesions are extremely rare. We report that a right-handed, 48-year-old man, who was hypertensive and diabetic but had no prior psychiatric history, developed severe personality changes and a frontal-like syndrome after recovery from acute-onset impairment of consciousness at the age of 43. Other neurological and neuropsychological disturbances, especially verbal and visual amnesia, were unremarkable. MRI showed a very small infarct in the left paramedian area of the thalamus, mainly involving the dorsomedial nucleus.
Oxidative Properties of Skin Exudates – A Determinant for Nickel Diffusion: A Review
Authors: Hostýnek Jurij J. , Reagan Katherine E. , Maibach Howard I.
Published: April 2003

Skin exudates can corrode (oxidize) and possibly dissolve metal surfaces they contact. Their composition varies as a function of physical, pharmacological and environmental conditions, gender, age, sweat rate, body site and methods of collection, also in a healthy organism. This overview includes sweat composition and discusses components which constitute the skin’s acid mantle: low-molecular-weight acids in sweat and fatty acids in sebum, with a particular potential to solubilize nickel-containing metal objects contacting skin. These components can form nickel salts whose molecular characteristics will determine the preferred route of penetration: either appendageal diffusion or through the intercellular lipid domains, besides the commonly assumed transcellular path. Considering the ease with which elicitation reactions set in when sensitized individuals contact nickel-releasing metal objects, these two alternatives appear to represent pathways which are more likely routes than the conventional transcellular diffusion, which takes a longer time to occur.
A Physicochemical Approach to Minimize the Irritant Capacity of Anionic Surfactants
Authors: Vilaplana J. , Lecha M. , Trullas C. , Coll J. , Comelles F. , Romaguera C. , Pelejero C.
Published: April 2003

Skin care companies try to find the best way for cutaneous hygiene in defective skin conditions. Novel strategies to ensure extra-mild non-soap surfactant cleansing products should be searched for and designed. Among possible strategies, the control of the physicochemical behaviour of surfactants in solution seems to be a promising approach to minimize their irritant properties. To assess this, we have tested – with 28 healthy volunteers by means of 48-hour patch testing – the irritant capacity of the following solutions: sodium lauryl sulphate (SLS) 1% w/w, disodium cocoyl glutamate (SCG) 1% w/w, sodium PEG-4 lauramide carboxylate (SLC) 1% w/w and the mixtures SLS 1% w/w + SCG 1% w/w and SLS 1% w/w + SLC 1% w/w. The cutaneous responses were evaluated by visual scoring and bioengineering measurements of transepidermal water loss, laser Doppler cutaneous blood flow and skin colour reflectance. The experimental values of all bioengineering end-points and visual scores have shown that the addition of co-surfactants to a constant dose of SLS produces a significant reduction of skin irritation notwithstanding an increase in the total surfactant concentration. The physicochemical studies show that the control of the physicochemical behaviour of surfactants in solution could be a promising approach to develop cleansing products with a less damaging effect on the skin.
Effect of Patient Weight on the Anticoagulant Response to Adjusted Therapeutic Dosage of Low-Molecular- Weight Heparin for the Treatment ofVenous Thromboembolism
Authors: Wilson S. Jo-Anne , Wilbur Kerry , Burton Erica , Anderson David R.
Published: April 2003

Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in obese patients are limited. Some manufacturers have recommended a maximum daily dose of LMWH not to be exceeded. The purpose of this study was to determine if body weight influenced the anticoagulant response to a weight-based dose of LMWH for the treatment of venous thromboembolism. Patients with serum creatinine levels <150 µmol/l receiving the LMWH , dalteparin 200 anti-Xa IU/kg based on actual body weight subcutaneously once daily for the treatment of deep vein thrombosis or pulmonary embolism, were eligible for the study. Patients received a minimum of 5 days LMWH treatment. Patients had peak anti-Xa levels (IL Test Chromogenic assay) measured 3–4 h following their day 3 injection and trough anti-Xa levels measured immediately prior to injections on day 3 and 5. No dose adjustments were made on the basis of the anti-Xa levels. Patients were a priori stratified into three weight classes: (A) within 20% of ideal body weight (IBW) (n = 13); (B) 20–40% of IBW (n = 14), and (C) greater than 40% of IBW (n = 10). The largest patient weighed 190 kg and had a body mass index of 58. Mean daily LMWH doses were 14,030, 17,646 and 23, 565 IU for groups A, B and C, respectively. Mean (SD) trough anti-Xa levels on day 3 were 0.12 (0.05) anti-Xa IU/ml for group A, 0.11 (0.03) anti-Xa IU/ml for group B and 0.11 (0.03) anti-Xa IU/ml for group C (p > 0.2). Similar trough anti-Xa levels were observed on day 5. Mean (SD) peak anti-Xa levels on day 3 were 1.01 (0.20) anti-Xa IU/ml, 0.97 (0.21) anti-Xa IU/ml and 1.12 (0.22) anti-Xa IU/ml for groups A, B and C, respectively (p > 0.2). No thromboembolic or bleeding complications occurred during LMWH therapy in any patients. These findings suggest that body mass does not appear to have an important effect on the response to LMWH up to a weight of 190 kg in patients with normal or near normal renal function.
Lebetin Peptides: Potent Platelet Aggregation Inhibitors
Authors: Marrakchi N. , Mabrouk K. , Regaya I. , Sarray S. , Fathallah M. , Rochat H. , El Ayeb M.
Published: April 2003

Lebetins from Macrovipera lebetina snake venom constitute a new class of inhibitors of platelet aggregation. There are two groups of peptides: lebetin 1 (L1; 11- to 13-mer) and lebetin 2 (L2; 37- to 38-mer). The short lebetins are identical to the N-terminal segments of the longer ones. They inhibit platelet aggregation induced by various agonists (e.g. thrombin, PAF-acether or collagen). The shortest lebetin (11-mer) shows potent inhibition of rabbit (IC50 = 7 nM) and human (IC50 = 5 nM) platelets. They prevent collagen-induced thrombocytopenia in rats. N- and C-terminal-truncated synthetic L1γ (sL1γ; 11-mer) is less active in inhibiting platelet aggregation than the native peptide. Results from Ala scan studies of the sL1γ peptide indicated that replacement of the residues (P3, G7, P8, P9 or N10) resulted in a remarkable drop in the activity, whereas replacement of residues K2, P4 or K6 by Ala resulted in enhancement of the antiplatelet activity by at least 10-fold. To examine the activity of multimeric L1γ, several multimeric peptides were synthesized using the multiple-antigen peptide system assembled on a branched lysine core and their antiplatelet activity was evaluated in vitro. The largest multimeric peptides showed a 1,000-fold increase in antiplatelet activity.
Procoagulant Proteins from Snake Venoms
Authors: Kini R. Manjunatha , Rao Veena S. , Joseph Jeremiah S.
Published: April 2003

Several procoagulant proteins from snake venoms have been isolated and characterized. They are either serine proteinases or metalloproteinases, which activate specific zymogens of coagulation factors and initiate the coagulation cascade. These procoagulant proteins are useful in treating various thrombotic and hemostatic conditions and contribute to our understanding of molecular details in the activation of specific coagulation factors. Recent studies have shown that the prothrombin activators with serine proteinase activity are structurally and functionally similar to mammalian coagulation factors. Their structural studies should provide us insight into prothrombinase complex formation. Here, we present an overview of snake venom procoagulant factors.
Emergence in Psychology: Lessons from the History of Non-Reductionist Science
Authors: Sawyer R. Keith
Published: April 2003

Theories of emergence have had a longstanding influence on psychological thought. Emergentism rejects both reductionism and holism; emergentists are scientific materialists, and yet argue that reductionist explanation may not always be scientifically feasible. I begin by summarizing the history of emergence in psychology and sociology, from the mid-19th century through the mid-20th century. I then demonstrate several parallels between this history and contemporary psychology, focusing on two recent psychological movements: socioculturalism and connectionist cognitive science. Placed in historical context, both socioculturalism and connectionism are seen to be revivals of 19th and early 20th century emergentism. I then draw on this history to identify several unresolved issues facing socioculturalists and connectionists, and to suggest several promising paths for future theory.
Increased Response of Plasma Allopregnanolone to Corticotropin-Releasing Hormone in Obese Patients
Authors: Menozzi Renata , Florio Pasquale , Bondi Mario , Luisi Stefano , Cobellis Luigi , Genazzani Andrea Riccardo , Del Rio Graziano , Petraglia Felice
Published: April 2003

Allopregnanolone is a neuroactive steroid present in the brain, but also measurable in systemic circulation. It exhibits anxiolytic and anticonvulsant effects and is able to produce hyperphagia. Since eating behavior disturbances and increased peripheral basal sympathetic activity have been reported in obese subjects, the present study investigated allopregnanolone and catecholamine (epinephrine and norepinephrine) responses to corticotropin-releasing hormone (CRH) in obese subjects. Blood was sampled from 39 obese (14 men and 25 women) and 57 normal-weight subjects (20 men and 37 women) and assayed for cortisol, allopregnanolone and catecholamines concentrations. In addition, 13 obese patients (5 men and 8 women) and 18 control subjects (9 men and 9 women) were submitted to a CRH test. Plasma allopregnanolone and norepinephrine levels were significantly higher in obese than in control subjects (p < 0.01), but plasma cortisol and epinephrine concentrations were comparable in both groups. No correlation was found in any group between plasma allopregnanolone and norepinephrine or epinephrine levels. Acute CRH administration significantly stimulated allopregnanolone secretion, with peak levels at 15 min in obese subjects, whereas maximal concentrations were reached after 60 min only in controls. In obese patients the allopregnanolone secretory incremental area was significantly higher than in controls (p < 0.02). CRH injection increased cortisol levels to a comparable extent in both groups. Plasma norepinephrine or epinephrine levels did were not significantly affected by CRH test in either group. In conclusion, obese subjects present higher allopregnanolone levels and a greater response to CRH than normal subjects. Since allopregnanolone has hyperphagic effects in rats, hypersecretion of the hormone in obese patients may represent one of the mechanisms underlying obesity.
Elevated Expression of Galanin Receptors in Childhood Neuroblastic Tumors
Authors: Berger Alexandra , Tuechler Camilla , Almer Dietmar , Kogner Per , Ratschek Manfred , Kerbl Reinhold , Iismaa Tiina P. , Jones Neil , Sperl Wolfgang , Kofler Barbara
Published: April 2003

The neuropeptide galanin (GAL) has been shown to be present in certain brain tumors. In order to learn more about GAL and its receptors in human tumors of the peripheral nervous system, we investigated the expression of the GAL peptide and the GAL receptors in tumor tissue from childhood neuroblastic tumors. GAL peptide concentrations up to 674 ± 166 fmol/mg of tissue were detected by radioimmunoassay, but no significant correlation with standard tumor markers or the prognosis of the 14 patients investigated was observed. Ligand binding experiments showed different levels of GAL binding in all 28 primary neuroblastomas and 7 ganglioneuromas investigated. All three human GAL receptor subtypes cloned to date could be detected, with the GALR1 receptor subtype being expressed most prominently. GAL binding did not significantly correlate with genetic markers such as unfavorable DNA ploidy, amplification of the oncogene MYCN and allelic loss of chromosome 1p. However, low galanin binding was significantly correlated with survival (p = 0.021) in this limited analysis of neuroblastic tumor samples. These results raise the possibility that the expression of GAL binding sites may play a role in neuroblastic tumor biology and behavior.
Suppressive Action of Orexin A on Pulsatile Luteinizing Hormone Secretion Is Potentiated by a Low Dose of Estrogen in Ovariectomized Rats
Authors: Furuta Miyako , Funabashi Toshiya , Kimura Fukuko
Published: April 2003

Orexins are hypothalamic neuropeptides which stimulate luteinizing hormone (LH) secretion in estrogen- and progesterone-treated ovariectomized (OVX) rats and suppress it in OVX rats not treated with estrogen, suggesting a modulation by estrogen of the response to orexins. We examined the effects of orexin A on pulsatile LH secretion in OVX rats treated with a very small dose of estrogen so as to maintain the pulsatile secretion of LH. The estrogen treatment was done 24 h before the blood sampling by subcutaneously implanting a silicone tube (id = 1.5 mm, od = 2.5 mm, length = 25 mm) containing 17β-estradiol (E2) dissolved in sesame oil at 20 µg/ml. In OVX rats treated with sesame oil as a control, the intracerebroventricular (icv) injection of orexin A (0.3 nmol, dissolved in 3 µl artificial cerebrospinal fluid) had no significant effect on the parameters of pulsatile LH secretion, i.e., pulse frequency and pulse amplitude, although it caused a small but statistically significant decrease in overall mean LH concentrations within 1 h. In OVX rats treated with E2, the icv injection of orexin A significantly suppressed the pulsatile LH secretion; the frequency decreased for more than 2 h, inducing a rapid decline in overall mean LH concentrations. In view of the finding that a much higher dose of orexin A suppresses pulsatile LH secretion in OVX rats not treated with E2, we suggest that the suppressive action of orexin A on pulsatile LH secretion is potentiated by estrogen.