bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of and Predicting Factors for Torsades de Pointes during Intravenous Administration of Amiodarone
Authors: Psirropoulos D. , Lefkos N. , Boudonas G. , Efthimiadis A. , Eklissiarhos D. , Tsapas G.
Published: April 2003

Objective: There is considerable knowledge of the incidence of torsades de pointes (TdP) during the administration of amiodarone The aim of our study was to determine the incidence of TdP during the loading phase of intravenous administration of amiodarone, intended to reverse paroxysmal atrial fibrillation (PAF) to sinus rhythm (SR), and to test the hypothesis that their prevalence is greater among women than men, as reported earlier. We also sought to determine factors predisposing to the occurrence of TpD, such as atrium size and hyperglycemia. Methods: We evaluated 189 patients (M = 107, F = 82, mean age = 56 ± 19 years), who were admitted for PAF, and for whom amiodarone was selected as the first-choice drug for PAF reversion. During the first 24 h of the loading phase (300 mg rapid i.v. administration within 20 min and 1,500 mg i.v. for 24 h) we recorded all ventricular arrhythmias. All patients were on anticoagulant treatment and all of them were evaluated for corrected QT (QTc), as well as additional risk factors (atrial size, serum glucose, hypopotassemia, hypomagnesemia, severe bradycardia). Patients with heart failure, hypertrophic obstructive cardiomyopathy, a history of coronary artery disease or ventricular tachycardia, as well as those treated with drugs prolonging the QT interval, were excluded from the study. Results: 108 patients (57.1%) experienced successful conversion of PAF into SR on amiodarone. Five patients (2.6%), all female, mean age 53.0 ± 1.2 years, developed TpD. All episodes occurred at the end of the loading phase (21–24 h) of amiodarone administration. None of them had hypopotassemia, hypomagnesemia, or bradycardia (HR <55 bpm). Two of the TpD patients had elevated glucose levels, and all of them had prolonged QTc immediately prior to the TpD. Conclusion: We confirm that women are at increased risk of developing TpD during the administration of amiodarone. TpD develop towards the end of the intravenous loading phase; the electrocardiographic changes should be closely monitored towards the end of the loading phase. The presence of diabetes mellitus or temporal hyperglycemia and prolonged QTc seems to be predicting factors for TpD during i.v. amiodarone administration.
Morbidity of Post-Coronary Artery Bypass Surgery Patients with Atrial Fibrillation Treated with Rate Control versus Sinus-Restoring Therapy
Authors: Shah Paresh , Shpigel Aleksandr , Wasser Thomas , Sabo Mary , Feldman Bruce
Published: April 2003

Background: Atrial fibrillation (AF) is the most common dysrhythmia encountered in the post-coronary artery bypass (post-CABG) patient, reported to occur with a frequency of 20–40%. To date, with the exception of amiodarone, there is no evidence that prophylactic therapy or therapy to restore and maintain sinus rhythm reduces the risk of adverse events associated with AF. Objective: To determine whether rate control alone is an effective method of managing post-CABG AF. Method: Prospective nonrandomized observational pilot study to assess the outcome of patients with post-CABG AF managed with rate control (group 1) or a combination of rate control and sinus-restoring therapy (group 2). Adverse events, postoperative length of stay, and persistence of AF were assessed in both groups at discharge and 30 days post-discharge. Results: Post-CABG AF was observed in 101 patients. Among the 39 patients in group 1 and 62 patients in group 2, there was an 87% spontaneous conversion rate to sinus rhythm at discharge (p = 0.99). The surgical length of stay was 6.3 days in group 1, and 8.3 days in group 2 (p = 0.01). Adverse events were observed in 2 patients (5.1%) in group 1, and 7 patients (11.3%) in group 2 (p = 0.29). Conclusion: Rate control appears to be an effective method of management of post-CABG AF patients, reducing length of hospital stay without increasing the rate of adverse events. Similar proportions of patients from both groups were in sinus rhythm at time of discharge, irrespective of therapeutic techniques.
Intima-Media Thickness Measurements in the Carotid and Femoral Artery as an Indicator of Symptomatic Coronary Atherosclerosis
Authors: Šrámek A. , Reiber J.H.C. , Rosendaal F.R.
Published: April 2003

Background: Ultrasonographically determined intima-media thickness of peripheral arteries is frequently used as an indicator of generalized and coronary atherosclerosis. Generally, the carotid artery is used. Measurements in the femoral artery have received little attention. Objective: In this study we investigated which of the ultrasonographically determined intima-media thickness measurements in either the common carotid artery, the carotid bulb, the common femoral artery or the superficial femoral artery is the best indicator for clinical coronary atherosclerosis. Methods: We determined the intima-media thickness in the common carotid artery, the carotid bulb, the common femoral artery and in the superficial femoral artery by B-mode ultrasonography in 78 patients with clinically proven severe coronary atherosclerosis and in 47 age-matched population controls. The odds ratio for the presence of coronary atherosclerosis was determined for every quintile of the intima-media thickness measurements in the arteries. Furthermore receiver operating characteristic (ROC) curves were constructed for the arteries to visualize the discriminating power of the measurements in these arteries. Results: For every quintile, the odds ratios (for the presence of clinical coronary atherosclerosis) of the measurements were the highest in the carotid bulb (range 3.7–7.1) and in particular in the common femoral artery (9.8–27.9). Inspection of the ROC curves showed that the test performance (i.e. sensitivity and specificity) to discriminate between individuals with clinical coronary atherosclerosis and the population controls was best for the femoral artery. The curves of the other three arteries were similar. Conclusion: The results of our study indicate that intima-media thickness measurements in the common femoral artery are a better indicator of coronary atherosclerosis than in the other three arteries.
Problems and Limitations of Meta-Analyses within the Framework of Evidence-Based Medicine
Authors: Kleist Peter
Published: April 2003

Within the framework of evidence-based medicine, meta-analyses represent a methodological tool to consolidate the state of knowledge on particular medical questions. However, meta-analyses per se already raise some fundamental problems. If quality criteria are not taken into account in the setting up of meta-analyses, this can result in methodological bias, so that in the final analysis, the intervention efficacy can be clearly underestimated or overestimated. Unfortunately, despite the existence of guidelines for their preparation, many published meta-analyses show considerable shortcomings as far as the methodology is concerned, and their value for the drawing up of diagnostic or therapeutic guidelines therefore has to be considered as questionable. Only a limited number of collaborative groups, for example the Cochrane Collaboration, set up meta-analyses with a high level of methodology. While their systematic reviews are to be recommended, the large number of published meta-analyses have to be viewed with scepticism, since often their results and conclusions cannot be comprehended objectively. In those areas of medicine where data and evidence are scanty, even meta-analyses cannot work wonders, because the value of a meta-analysis depends entirely on the value of the individual studies. Therefore, randomised, controlled studies will in future continue to play the decisive role in finding answers to the existing medical questions – and meta-analyses can help to formulate the right questions.
Immunomodulation by Opioid Peptidomimetic Compound
Authors: Narayan Prem , Singh Vijay K. , Agarwal Shyam S. , Tandon Ruchi , Haq Wahajul , Raghubir Ram , Dhar Manojit M.
Published: April 2003

Objective: As a follow-up to our earlier studies on immunomodulation with opioid peptides, we synthesized and evaluated immunomodulatory activity of four peptidomimetic compounds, i.e. Tyr-NH-C(Me)2-CH2-O-Phe-NH2 (1), Tyr-NH-C6H5-(o)-CH2-CH2-O-Phe-NH2 (2), Tyr-NH-CH2-CH2-O-Phe-NH2 (3) and Tyr-NH-CH(D-Et)-CH2-O-Phe-NH2 (4). Methods: These compounds were synthesized in solution phase and evaluated for their immunomodulatory properties in vitro by mixed lymphocyte reaction (MLR), proliferation of opioid receptor-expressing cells, production of tumor necrosis factor-α (TNF-α) and nitric oxide. Results: This study shows the immunosuppressive potential of synthetic peptidomimetic compound 3. This compound inhibited two-way MLR and suppressed the proliferation of the µ-opioid receptor expressing human embryonic kidney cells HEK 293 in vitro. Inhibition of MLR by compound 3 was reversed by naloxone (opioid receptor antagonist) and β-funaltrexamine hydrochloride (µ-opioid receptor antagonist). The immunosuppressive effect of compound 3 was further demonstrated by inhibition of TNF-α and nitric oxide production in lipopolysaccharide-stimulated human PBMCs and mouse macrophage cells RAW 264.7, respectively. Conclusion: These observations suggest that compound 3 inhibits MLR through µ-opioid receptor present on cells.
Effect of Mycoplasma fermentans on Brain PGE2: Role of Glucocorticoids and Their Receptors
Authors: Wohlman Avital , Yirmiya Raz , Gallily Ruth , Weidenfeld Joseph
Published: April 2003

Objectives: Mycoplasmas are a group of eubacteria, which cause various diseases in animals and in humans, and can contribute to diseases produced by other infectious agents, particularly HIV. We have recently reported that intracerebral administration of Mycoplasma fermentans (MF) produces both neuroendocrine and behavioral alterations. Some of these responses were mediated by MF-induced production of prostaglandin E2 (PGE2). The aim of this study was to examine the role of glucocorticoids (GC) in regulating MF-induced brain prostaglandin production. Methods: Male rats were injected intracerebroventricularly with various doses of heat-inactivated MF, LPS or IL-1β and the following parameters were measured: (1) ex vivo production of hippocampal PGE2, (2) serum levels of ACTH and corticosterone, and (3) binding capacity of [3H]-dexamethasone (DEX) to hippocampal cytosol. Results: MF caused a small increase in hippocampal PGE2 production, but higher doses failed to produce a further increase. In contrast, the effects of LPS or IL-1β on PGE2 were dose-dependent. Removal of circulating GC by bilateral adrenalectomy significantly enhanced MF-induced brain PGE2 production. The three immune stimulators increased serum levels of ACTH and corticosterone to the same extent. Finally, MF, but not IL-1β increased the specific binding of [3H]-DEX to hippocampal cytosol. Conclusions: Brain PGE2 induced by MF is regulated by endogenous GC. These hormones have an attenuating effect on PGE2 production, probably through an MF-induced increase in GC binding by brain tissue. This mechanism may be important in the pathological effect of MF within the brain of AIDS patients.
An Age-Related Decline in Interleukin-10 May Contribute to the Increased Expression of Interleukin-6 in Brain of Aged Mice
Authors: Ye Shi-Ming , Johnson Rodney W.
Published: April 2003

Objectives: The DNA-binding activity of nuclear factor ĸB (NFĸB) is elevated in brain of aged mice, resulting in elevated levels of the inflammatory cytokine interleukin (IL)-6. The purpose of this study was to determine if in the brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes to the increase in IL-6. Methods: In initial studies coronal brain sections and glial cells from adult (6-months-old) and aged (24-months-old) mice were incubated in the presence or absence of lipopolysaccharide (LPS) and the concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent studies, the effect of recombinant murine IL-10 on constitutive and inducible NFĸB activity, IL-6 mRNA expression and IL-6 protein secretion by glia cultured from brains of adult and aged mice was determined. Results: Coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. This effect of age was evident in the absence and presence of LPS and suggested that a decrease in IL-10 production permitted increased IL-6 production. Consistent with this idea, treatment of glia from aged mice with recombinant IL-10 decreased both constitutive and inducible binding of NFĸB to the IL-6 gene promoter. The decrease in NFĸB activity was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10, however, had no effect on NFĸB activity, which was undetectable in unstimulated glia from adult mice, and did not decrease steady-state levels of IL-6 mRNA or IL-6 protein secretion. Conclusions: Collectively, these studies suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in the aged brain it decreased and thus enabled a cascade of intracellular events that increased expression of the IL-6 gene.
Plasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder
Authors: Baker Dewleen G. , Ekhator Nosa N. , Kasckow John W. , Hill Kelly K. , Zoumakis Emmanouil , Dashevsky Boris A. , Chrousos George P. , Geracioti Jr. Thomas D.
Published: April 2003

Background: Interleukin-6 (IL-6) secretion is suppressed by glucocorticoids and stimulated by catecholamines. Patients with posttraumatic stress disorder (PTSD) have decreased cortisol and increased catecholamine secretion. The purpose of this study was to assess the relation of IL-6 levels and hypothalamic-pituitary-adrenal and noradrenergic activity in patients with well-characterized PTSD. Methods: Cerebrospinal fluid (CSF) was withdrawn via a lumbar subarachnoid catheter over 6 h from 11 combat veterans with PTSD and 8 age- and sex-matched healthy controls. Blood was withdrawn concurrently. We measured IL-6, CRH and norepinephrine concentrations in the CSF and IL-6, ACTH, cortisol and norepinephrine in plasma. Results: Mean and median CSF IL-6 concentrations were higher in PTSD than in controls (mean = 24.0 vs. 14.6, p = 0.05; median = 26.7 vs. 14.3, p < 0.03): plasma IL-6 concentrations, however, were not different between the two groups. Plasma IL-6 and norepinephrine were positively correlated in the PTSD group (r = +0.74, p < 0.04), but not in normals (r = –0.55, p = 0.20). Conclusions: PTSD patients have increased CSF concentrations of IL-6. Their plasma IL-6 is not elevated but is more tightly associated with noradrenergic output in these patients than in normals. Both findings might be explained by the low cortisol secretion previously reported in PTSD as a result of lowered glucocorticoid suppression of IL-6 secretion. High levels of CSF IL-6 may reflect neurodegeneration or compensatory neuroprotection.
Inhibitory Effect of Ibudilast on Urinary Albumin Excretion in Type 2 Diabetes mellitus with Microalbuminuria
Authors: Hoshino Tazue , Ikeda Tadasu
Published: April 2003

To evaluate the clinical effect of ibudilast, a prostacyclin-mediated vasodilator and antiplatelet agent, on diabetic nephropathy, 8 nonhypertensive patients with type 2 diabetes mellitus (DM; 4 men and 4 women, mean age: 58.9 ± 11.4 years, duration of diabetes: 16.9 ± 3.2 years) with microalbuminuria [20–200 mg/g creatinine (Cr)] were administered ibudilast (30 mg/day) for 18 months (ibudilast group). The urinary albumin excretion index (UAE, mg albumin/g Cr) was compared with 8 age-matched type 2 DM with microalbuminuria (control group). During the study, the UAE significantly decreased in the ibudilast group, while it significantly increased in the control group. After 18 months, the UAE (52 ± 19 mg/g Cr) in the ibudilast group was significantly (p < 0.05) lower than that (99 ± 46 mg/g Cr) in the control group. These results suggest that ibudilast may inhibit the progression of early diabetic nephropathy in type 2 DM.
Dietary Quercetin Augments Activator Protein-1 and Does Not Reduce Nuclear Factor-κB in the Renal Cortex of Rats with Established Chronic Glomerular Disease
Authors: Rangan Gopala K. , Wang Yiping , Harris David C.H.
Published: April 2003

Background/Aims: Quercetin, a naturally occurring dietary flavonoid, is a potent in vitro inhibitor of the transcription factors, nuclear factor (NF)-ĸB and activator protein (AP)-1. Here we investigated the efficacy of quercetin to suppress renal cortical NF-ĸB/AP-1 activation and tubulointerstitial injury, in vivo, in a nephrotic rat model of chronic glomerular disease. Methods: Adult male Wistar rats with (n = 27) or without (n = 15) Adriamycin nephropathy (AN) were stratified into six groups (according to proteinuria and endogenous creatinine clearance, measured on day 10) and pair-fed a semipurified diet supplemented with or without quercetin (0.5, 2%) from day 14 to 36. Results: Quercetin-fed rats had minimal weight gain during the study (p < 0.05). In AN, proteinuria, the decline in endogenous creatinine clearance, hypercholesterolaemia and cortical tubulointerstitial injury were not reduced by quercetin. Quercetin had no effect on renal cortical NF-ĸB activation, but unexpectedly exacerbated the induction of AP-1 in AN (by 67%, p < 0.05). In normal rats, quercetin increased proteinuria (by 75%, p < 0.05), renal cortical AP-1 activation (by 198%, p = 0.06), and malondialdehyde production (by 110%, p < 0.05). Conclusion: These data suggest that supplementation of the diet with quercetin is not an effective therapeutic strategy alone to reduce NF-ĸB/ AP-1 activation in chronic glomerular diseases, and paradoxically could be associated with adverse renal effects.
Remission of Nephrotic Syndrome due to AA Amyloidosis and Initiation of Glomerular Repair after Surgical Resection of Localized Castleman’s Disease
Authors: Mandreoli Marcora , Casanova Silvia , Vianelli Nicola , Pasquali Sonia , Zucchelli Pietro
Published: April 2003

To shed further light on the eventual destiny of amyloid kidney deposits after interruption of amylogenic stimulus, we report a case of a 47-year-old woman with nephrotic syndrome due to renal amyloidosis, complicating abdominal Castleman’s disease. After 5 courses of therapy with melphalan and prednisolone which failed to improve the nephrotic syndrome or her general clinical condition, and 1 year after the diagnosis of renal amyloidosis, surgical excision of the abdominal mass was performed. Whereas her clinical symptoms and other laboratory findings rapidly improved, the proteinuria took 18 months to disappear. A second renal biopsy, performed 30 months after surgical resection, showed persistence of the amyloid deposits in the same extent. However, electron microscopy revealed subtle reparative phenomena at the epithelial site of the basement membrane. We conclude that proteinuria associated with amyloidosis does not only depend on structural damage and that the new synthesized segment of basement membrane observed by us probably represents a mechanism of repair and the start of a long healing process.
Genomic Analysis of Idiopathic Infertile Patients with Sperm-Specific Depletion of CD46
Authors: Nomura Midori , Kitamura Masaya , Matsumiya Kiyomi , Tsujimura Akira , Okuyama Akihiko , Matsumoto Misako , Toyoshima Kumao , Seya Tsukasa
Published: April 2003

Three infertile subjects with no expression of CD46 (membrane cofactor protein of complement) on their spermatozoa were found when screening 542 idiopathic male infertile patients. The sperm CD46 isoform was reported to be associated with the sperm-egg interaction, yet a ubiquitous expression of CD46 confers resistance to complement-mediated injury on host cells. All three patients expressed normal CD46 isoforms on their lymphocytes and granulocytes. Thus, the loss of CD46 is sperm-specific, probably due to testicular germ cell-specific regulation of CD46 production. Recently, a mechanism of the gene regulation of human CD46 was elucidated in which the silencer element of the 3′ UT and the promoter region of human CD46 gene partly participate. Here, we analyzed these regions of the CD46 gene in our 3 patients. We found no abnormality in 3′ and 5′ regions of the CD46 genome in the 3 patients. Thus, in these infertile patients sperm-specific depletion of CD46 is not governed by the so for identified regulators in the CD46 gene. Other unknown factors outside the known regulatory regions would play a role in the regulation of sperm-specific CD46 expression.
Caries-Preventive Effects of Fluoride Products when Used in Conjunction with Fluoride Dentifrice
Authors: Zimmer Stefan
Published: April 2003

Toothbrushing with fluoride dentifrice has become an important public health measure in preventing caries and gingivitis. Since the fluoride concentration in dentifrices does not provide absolute protection for everyone and is limited by legal regulations, the question about the efficacy of additional use of topical fluoride products arises. In children aged 9–15 years, the biannual application of Duraphat® varnish in school-based programmes provides a caries inhibition of 38%. A caries inhibition of up to 40% can also be achieved by gels containing 1.25% fluoride, if applied 30 times per year. In subjects with a risk of root caries, the daily use of a 250-500 ppm fluoride solution seems to be advisable.
The Influence of Different Fluoride Compounds and Treatment Conditions on Dental Enamel: A Descriptive in vitro Study of the CaF2 Precipitation and Microstructure
Authors: Petzold Matthias
Published: April 2003

Electron and atomic force microscopy techniques have been applied to characterize both the in vitro deposition intensity and the microstructure of the KOH-soluble fluoride precipitates on human dental enamel. The study was focused on the effects of amine fluoride, sodium fluoride and sodium monofluorophosphate having a fluoride concentration of 0.1% F in acidulated and aqueous solutions. Under certain conditions, fluoride globules were formed within an initiation time of less than 20 s. This result supports the potential significance of this process for the cariostatic action of fluorides during dentifrice use. The deposition intensity seems to be dependent on the availability of Ca and F ions on the dental surface. A nanocrystalline calcium fluoride-like microstructure was revealed, with an additional phosphorus and oxygen incorporation as a function of the treatment time.
What Is the Optimum Fluoride Concentration Needed for the Remineralization Process?
Authors: Hellwig E. , Lussi A.
Published: April 2003

In vitro experiments could demonstrate that only negligible amounts of fluoride are necessary to promote remineralization of incipient caries lesions. From the clinical point of view, there is evidence that only under certain circumstances is a stabilization of the surface zone of an incipient caries lesion the true mechanism of action of topically applied fluorides. However, an optimum universally valid fluoride concentration needed for this process cannot be defined.
Automated Three-Dimensional Signature Model for Assessing Brain Injury in Emergent Stroke
Authors: Welch K.M.A. , Nagesh V. , D’Olhaberriague L.D. , Zhang Z.G. , Boska M.D. , Patel S. , Windham J.P.
Published: April 2003

This presentation will focus on the value of established and newer MR methods that can be applied to the diagnosis and management of ischemic stroke with emphasis on future applications of MR to provide previously unmet needs of the treating clinician and clinical trials. Time alone is an inadequate indicator of the therapeutic window, especially when the time of stroke onset is uncertain. Thus, there is a need to predict the evolution of stroke in a way that more precisely and with greater resolution identifies the progression of cellular damage at the moment of investigation. This also would be of value for thrombolysis when knowledge of the degree and extent of tissue necrosis and the consequent potential for brain hemorrhage is of the utmost importance. To provide this, we perform postprocessing of diffusion-, T1- and T2-weighted images to produce the apparent diffusion coefficient of water, and T1 and T2 maps that are then further processed to provide maps and quantitation of the tissue signatures of ischemic histopathology. By these means, we can accomplish objective volumetric analysis of infarct size and of the proportions of potentially viable and salvageable tissue. We will show how this has the potential to predict long-term stroke outcome and facilitate decision-making in terms of safety of reperfusion strategies and the appropriateness of cytoprotective treatment. The value of our approach is to replace time as the therapeutic window and extend the opportunity of treatment to those patients presenting beyond the stringent time limits employed in current investigative clinical trials. Further, used as a surrogate marker of clinical outcome, this form of stroke analysis may speed proof of principle clinical trials in small numbers of stroke patients.
Acute Care in Stroke: Do Stroke Units Make the Difference?
Authors: Díez-Tejedor E. , Fuentes B.
Published: April 2003

The consideration of stroke as a medical emergency and the development of new specific treatments to be applied in a narrow therapeutic window have shown the need to establish an adequate organization system for the management of stroke. It should be considered as an integral process both outside and inside the hospital. General care is essential and must already start outside the hospital, and comprises respiratory and cardiac care, fluid and metabolic management, especially blood glucose control, avoiding the administration of glucose solutions, blood pressure control, early treatment of hyperthermia and prevention and treatment of neurologic and systemic complications. In the early 70s, the first stroke units (SU) were established as intensive-care SU, but failed to show improvement in terms of reduction of mortality-morbidity. Nowadays, the concept has changed to a non-intensive-care SU. The benefit of these SU has been amply demonstrated in terms of reduction in mortality and in long institutionalization, as well as better functional outcome compared with general wards, and the efficacy of a neurology ward compared to a general medicine department has also been shown, but at the moment there are no studies analyzing the differences between a stroke team (ST) in a department of neurology and a SU. In this regard, we have performed a sequential analysis comparing both SU and ST and demonstrated a reduction in length of stay, complications and acute care costs with an improvement in functional state at hospital discharge, a reduction in the discharge to nursing homes with an increase in patients translated into rehabilitation wards. With these data, we can conclude that SU, not ST are the most effective organizational model for acute stroke management. Definitely, the SU make the difference.
Recent Progress in Drug Treatment for Acute Ischemic Stroke
Authors: Devuyst G. , Bogousslavsky J.
Published: April 2003

The publication of the positive results of the National Institute of Neurological Disorders and Stroke (NINDS) trial of alteplase (a recombinant tissue plasminogen activator; rt-PA) for acute stroke patients in 1995 and its approval by the US Food and Drug Administration as well as the American Academy of Neurology and American Heart Association increased the interest and attention of the medical community in acute stroke treatment. However, the implication of this NINDS Stroke Study and other thrombolytic trials in clinical practice remains controversial and debated. Furthermore, the recent publication of the results from the European Cooperative Acute Stroke Study II (ECASS II) and Alteplase Thrombolysis of Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) studies will feed the controversy, since the results of these two studies are disappointing and do not confirm the positive results of the NINDS Stroke Study as expected by clinicians managing patients with acute stroke. The Standard Treatment with Alteplase to Reverse Stroke (STARS) and Cleveland studies, which involved a large number of community hospitals to assess the safety profile and the benefit of rt-PA thrombolysis for acute stroke patients in clinical practice, have shown controversial results. Consequently, the issue arises of which is the more reasonable position concerning thrombolysis by alteplase, which seems to work but has not been proven yet beyond reasonable doubt? The recent publication of the results from the Prolyse in Acute Cerebral Thromboembolism (PROACT II) study has shown that intra-arterial thrombolysis with prourokinase is a benefit treatment in stroke patients with a proven middle cerebral artery occlusion within 6 h of stroke onset. Numerous trials devoted to neuroprotection against acute ischemic stroke have been prematurely stopped because of safety concerns or poor risk-benefit ratios, but some new neuroprotective drugs seem promising and are being tested in ongoing studies. The third issue under study concerns the use of antithrombotic drugs in the acute phase of stroke, particularly the new potent platelet glycoprotein IIb/IIIa antagonists such as abciximab. In this paper, we have reviewed selected recent clinical trials focusing on recent advances in acute stroke therapy.
Antiplatelet Drugs: How to Select Them and Possibilities of Combined Treatment
Authors: Bornstein Natan M.
Published: April 2003

Antiplatelets are the pivotal drugs in preventing recurrent stroke or other major vascular events in patients who have undergone TIA or stroke. Aspirin is the most widely used, although its effect is very modest (relative risk reduction 20%), and most physicians use between 100 and 325 mg daily as a maintenance dose. For patients who develop stroke on aspirin treatment, the options are either to increase the dose of aspirin or to administer another anti-aggregate. No study has yet been performed to support these approaches. In patients who cannot tolerate aspirin, the options are clopidogrel 75 mg once daily or dipyridamole 400 mg combined with 50 mg aspirin. An approach which is very appealing, but not yet proven is to combine different antiplatelet drugs with different modes of action, such as aspirin and clopidogrel, in order to achieve a better and more effective antithrombotic effect. Further controlled trials are needed to justify this approach.
On the History of Lacunes, Etat criblé, and the White Matter Lesions of Vascular Dementia
Authors: Román Gustavo C.
Published: April 2003

The history of lesions associated with vascular dementia (17th to 19th century) is reviewed. Recognition of ischemic and hemorrhagic stroke types dates back to the 17th century; however, at that time a third type (‘cerebral congestion’) emerged as the most common form of apoplexy. This entity vanished as arterial hypertension became established with the introduction of the sphygmomanometer (1905). Before the 19th century, apoplexy was considered a uniformly fatal disease, although Willis first recognized post-stroke dementia in 1672. Dechambre (1838) first reported ‘lacunes’ in stroke survivors with small cerebral softenings. Durand-Fardel (1842) described interstitial atrophy of the brain (leukoaraiosis) and état criblé (cribriform state) reflecting chronic cerebral congestion. In 1894, Alzheimer and Binswanger identified ‘arteriosclerotic brain atrophy,’ a form of vascular dementia characterized by ‘miliary apoplexies’ (lacunes). Also in 1894, Binswanger described the disease that now bears his name. In 1901, Pierre Marie coined the name état lacunaire (lacunar state) for the clinical syndrome of elderly patients with multiple lacunes.
Pathophysiology of Age-Related Cerebral White Matter Changes
Authors: Pantoni Leonardo
Published: April 2003

The pathogenesis of age-related cerebral white matter changes (WMC) is still a matter of investigation. Alterations of deep small vessels, such as arteriolosclerosis, are considered to play a central role in the development of WMC. Stenosis or occlusion of small vessels may cause sudden or more chronic ischemia resulting in small areas of necrosis (lacunar infarction) or diffuse alterations consistent with the definition of white matter incomplete infarct. Moreover, the arteriolosclerotic changes may cause loss of autoregulation in the deep white matter and consequent cerebral blood flow fluctuations in response to changes of systemic blood pressure. Both these types of mechanisms may be particularly harmful because the blood supply of the white matter is of the terminal type with scarce anastomoses. Other pathophysiological hypotheses on the origin of WMC have been raised, and they can probably be considered as complementary to the ischemic one. The small vessel alterations could lead to damage of the blood-brain barrier and chronic leakage of fluid and macromolecules in the white matter. The increased interstitial fluid concentration in abnormal white matter may be also a consequence of arterial hypertensive bouts. Genetically determined factors could play an important role in the development of WMC, and at least one disease (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy – CADASIL) characterized by severe leukoencephalopathy exists with a determined genetic origin. It is possible that other genetic factors contribute, by interaction with conventional risk factors, to the development of white matter injury in nonfamilial cases.
Cognition and White Matter Lesions
Authors: Desmond David W.
Published: April 2003

Although it is recognized that ischemic stroke is a potent risk factor for vascular dementia, the influence of white matter lesions (WML) on cognitive function is less clear. In community-based MRI studies that have administered mental status tests to subjects who were free of clinically evident neurologic disease, a weak relationship between WML and generalized cognitive function has been reported. In studies that have administered neuropsychological test batteries, a stronger and more specific association has been recognized between WML and deficits in executive function, most likely due to the involvement of frontal-subcortical pathways. Cognitive deficits may be related to the total volume of the WML, with a threshold perhaps needing to be surpassed before such deficits are evident, but it is likely that the location of the WML also plays a role, with that threshold varying in association with the distribution of the lesions. Potential confounders of the results of previous studies include small, strategically located subcortical infarctions that may be masked by more extensive WML and other comorbid neurologic disorders, particularly Alzheimer’s disease. Future studies should be prospective, utilize standardized methods for structural and functional brain imaging, and administer comprehensive neuropsychological assessments in order to more rigorously investigate the relationship between evolving WML and declining cognitive functions.
In situ Activated Intestinal T Cells Expanded in vitro – without Addition of Antigen – Produce IFN-γ and IL-10 and Preserve Their Function during Growth
Authors: Agnholt Jørgen , Kaltoft Keld
Published: April 2003

Objective: The balance between mucosal CD4+ T cells producing IFN-γ or IL-10 is essential in the maintenance of intestinal homeostasis. We aimed to investigate how in situ activated T cells were expanded in vitro according to a new cell culture protocol and if it selected for continuous clonal CD4+ T cells capable of producing mainly IFN-γ or IL-10. Methods: T cell cultures were established from colonic biopsy specimens of 27 patients with Crohn’s disease and from 10 healthy controls in a medium supplemented with IL-2 and IL-4 but without addition of exogenous antigen or mitogen. Cytokine production was measured after stimulation (IL-12, super antigen) and inhibition (ciclosporin and methylprednisolone). Results: Cytokine production was increased in cultures from patients with Crohn’s disease compared to controls (IFN-γ, p = 0.005; IL-10, p = 0.003; TNF-α, p = 0.03). Early cultures were highly responsive to IL-12 stimulation. We established CD4+ T-cell clones escaping cellular senescence with an inflammatory or regulatory cytokine profile. Discussion: The data indicate that cultures of in situ activated inflammatory and regulatory subpopulations of intestinal T lymphocytes with pathogenic importance in Crohn’s disease can be established preserving their functional properties during growth.
Use of Human Recombinant DNase I Expressed in COS-7 Cells as an Immunogen to Produce a Specific Anti-DNase I Antibody
Authors: Takeshita Haruo , Yasuda Toshihiro , Nakazato Emiko , Nakajima Tamiko , Mori Shinjiro , Mogi Kouichi , Kaneko Yasushi , Iida Reiko , Kishi Koichiro
Published: April 2003

To obtain human deoxyribonuclease I (DNase I) as an immunogen, we have developed a procedure that is more useful and effective than the conventional procedure, which uses human urine as a starting material. In the new procedure, we culture COS-7 cells transfected with expression vector carrying human DNase I cDNA, and then purify the enzyme from the culture medium. The enzyme can be easily isolated to apparent homogeneity by passage through only three chromatography columns. The rabbit antiserum that we used against the recombinant DNase I was not inferior to that used against DNase I from human urine, in terms of both its ability to discriminate DNase I phenotypes and its ability to neutralize enzyme activity. Therefore, our procedure may be useful for producing an antibody specific for human DNase I.
Nomenclature and Overview of the Mouse (Mus musculus and Mus sp.) Immunoglobulin Kappa (IGK) Genes
Authors: Martinez-Jean Christèle , Folch Géraldine , Lefranc Marie-Paule
Published: April 2003

‘Nomenclature and overview of the mouse (Mus musculus and Mus sp.) immunoglobulin kappa (IGK) Genes’, the 19th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the mouse (M. musculus) IGK genes. The mouse (M. musculus) locus spans 3,200 kb. The total number of mouse (M. musculus) IGK genes per haploid genome is 164 (174 if the orphons are included). The functional genomic repertoire comprises 93 IGKV belonging to 18 subgroups, 5 IGKJ and 1 IGKC gene. IMGT gene names and definitions of the mouse (M. musculus) IGK genes on chromosome 6 and IGK orphons are provided with the gene functionality and the number of alleles, according to the concepts of IMGT-ONTOLOGY and to rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences. These tables and figures are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.
Comparison of Long-Term Monitoring Methods for Bipolar Affective Disorder
Authors: Hörn M. , Schärer L. , Walser S. , Scherer-Klabunde D. , Biedermann C. , Walden J.
Published: April 2003

Long-term monitoring is a clinical necessity in bipolar affective disorder. The most important requirements are usability and value for clinical decisions. Four methods of long-term monitoring – (1) the Adjective Mood Scale by von Zerssen, (2) Kraepelin’s early life charts, (3) the NIMH Life Chart Method by Leverich and Post and (4) the Social Rhythm Metric by Monk – were compared regarding the acceptance by patients, the time commitment needed for documentation and training as well as the usability for the clinician regarding psychotherapy and decision support in pharmacotherapy. The Adjective Mood Scale is easiest to learn, Kraepelin’s life chart offers the best graphical presentation, the NIMH life charts offer the best clinical decision support and the Social Rhythm Metric integrates a psychotherapeutic approach.
Clinical Subtypes of Schizophrenic Disorders: A Cluster Analytic Study
Authors: Lykouras Lefteris , Oulis Panayotis , Daskalopoulou Eugenia , Psarros Konstantin , Christodoulou George N.
Published: April 2003

Two hundred and fifty-five psychiatric inpatients with a definite diagnosis of DSM-IV schizophrenic disorder were examined by means of the Structured Clinical Interview and rated on the 30 main items of the Positive and Negative Syndrome Scale (PANSS). Patients’ scores were subjected to a cluster analysis, using Ward’s method. Cluster analysis indicated the existence of five groups. The first group (n = 46) comprised patients with overall psychopathology of minimal severity, the second group (n = 39) patients with severe positive symptoms along with symptoms of psychomotor excitement, the third group (n = 58) patients with severe positive psychopathology only, the fourth group (n = 34) patients with severe positive negative depressive and cognitive symptoms and, finally, the fifth group (n = 78) patients with severe negative symptoms only. Patients in the first and third groups were older and their illnesses were of longer duration compared to those of the remaining groups. With respect to DSM-IV clinical types of schizophrenic disorders, the paranoid type predominated in the second and the third groups, whereas the disorganized and catatonic types were markedly overpresented in the fifth group.
Schizophrenic Disorders among Turkish Migrants in Germany
Authors: Haasen Christian , Yagdiran Oktay , Mass Reinhard , Krausz Michael
Published: April 2003

Several studies have implied cultural differences in the psychopathology of schizophrenia between migrants and natives. In a diagnostically strictly controlled study, including comparison of diagnosis with a Turkish-speaking psychiatrist, 74 patients of Turkish and 48 of German origin, all with a diagnosis of schizophrenic disorder, were compared using PANSS and HAM-D. The Turkish sample showed higher depression and hostile excitement, even in the subsample of those with paranoid schizophrenia, and no differences in positive, negative or cognitive symptoms. The similarities especially concerning core symptoms reflect evidence from cross-cultural studies on schizophrenia. In conclusion this study shows main differences in psychopathology between psychotic migrants and natives, as discussed in the literature, may be mainly due to diagnostic differences.
Relationship between Cannabis Use, Schizotypal Traits, and Cognitive Function in Healthy Subjects
Authors: Mass Reinhard , Bardong Christina , Kindl Korana , Dahme Bernhard
Published: April 2003

This research examined the relationship between cannabis use and schizotypal features. A sample of cannabis users (n = 20) was compared with a matched control group (n = 20). All participants were male students of the University of Hamburg. Subjects completed the Perceptual Aberration Scale and the Schizotypal Personality Questionnaire. A Negative Priming procedure and the Trail Making Test were carried out. A urine sample was obtained from each subject. Cannabis users exceeded controls in schizotypy scores and showed impaired neuropsychological parameters. Only within the cannabis group schizotypy scores correlated with neuropsychological parameters. Furthermore, cannabis users reported more often high-risk factors than controls. These findings indicate that among cannabis users there is an increased number of subjects with schizotypal features; schizotypal subjects seem to be more likely to use cannabis than the general population. Therefore, cannabis use may be a vulnerability indicator for schizophrenia.
ICD-10 Mild Cognitive Disorder following Meningitis due to Neurosarcoidosis
Authors: Prüter Christian , Kunert Hanns-Jürgen , Hoff Paul
Published: April 2003

We report the case of a patient referred to our department with the diagnosis of conversion disorder, who ultimately proved to have neurosarcoidosis presenting with mild cognitive disorder. Despite the criticism of mild cognitive disorder as a diagnostic entity, our patient met the criteria for it. The reported case exemplifies the difficulties in classifying mild cognitive deficits in patients suffering from brain diseases without major morphological damage.
The Validation of the Posttraumatic Stress Disorder Checklist Scale in Posttraumatic Stress Disorder and Nonclinical Subjects
Authors: Ventureyra Valérie A.G. , Yao Sai-Nan , Cottraux Jean , Note Ivan , De Mey-Guillard Chantal
Published: April 2003

Background: The Posttraumatic Stress Disorder Checklist Scale (PCLS) is a short self-report inventory for assessing the 3 main syndromes of Posttraumatic Stress Disorder (PTSD). The aim of this study was the validation of the French version of the PCLS in PTSD subjects and nonclinical subjects. Methods: One-hundred and thirteen outpatients suffering from PTSD according to DSM-IV were administered the PCLS. The patients’ scores on the PCLS were then compared to those of 31 nonclinical control subjects. Thirty-five of the patients were administered the PCLS twice over an interval of 1–2 weeks and also completed questionnaires measuring depression, phobia and anxiety. Results: The patients’ total score and subscores on the PCLS were found to be significantly higher than those of control subjects. The cutoff score of 44 on the French version PCLS distinguishes well between the PTSD group and control group with a high diagnostic efficacy (0.94). Factor analysis revealed 3 main factors corresponding to the reexperiencing, numbing and hyperarousal syndromes. The PCLS showed satisfactory test-retest reliability and internal consistency. Conclusions: The PCLS is therefore a valid and effective measurement of PTSD. It may be a useful tool for screening and assessing PTSD in psychiatric as well as in primary-care settings.
Increased Thymidylate Synthase mRNA Concentration in Blood Leukocytes following an Experimental Stressor
Authors: Ehrnrooth Eva , Zacharia Robert , Svendsen Gunner , Jørgensen Michael M. , Yishay Maya , Sørensen Boe S. , Hjelm Poulsen Jørgen , von der Maase Hans
Published: April 2003

Background: While it is well documented that immune responses, e.g. proliferative responses, can be influenced by psychosocial factors, e.g. stress, less is known about the biological mechanisms mediating such influences. The aim of the present investigation was to study the effect of an experimental stressor on mRNA levels in peripheral blood leukocytes of thymidylate synthase (TS), a gene necessary for cell division, while investigating possible individual differences in stress reactivity. Methods: Fifteen healthy subjects were investigated under three experimental conditions: (1) exposure to a computerized mental stressor; (2) relaxation, and (3) control. Measurements included TS mRNA levels, total leukocyte number, leukocyte subtypes, and serum cortisol before (baseline), immediately after, and 1 h after each experimental condition. Results: While no significant differences were found between experimental conditions at baseline in cortisol (p = 0.9) or TS mRNA levels (p = 0.1), significantly higher TS mRNA expression was found immediately after stress compared to pretreatment levels (p < 0.02). Changes in cortisol levels indicated an effect of the experimental stressor, with higher cortisol levels seen immediately after stress as compared to both relaxation (p < 0.01) and control (p < 0.01). Subjects who scored above the median on the Tellegen Absorption Scale showed significantly (p < 0.05) greater increases in cortisol and percentage of lymphocytes and significantly greater decreases in percentage of neutrophil cells after stress. Conclusion: The results suggest that TS mRNA levels in peripheral leukocytes may be sensitive to mental stress and confirm previous findings indicating that subjects scoring high on the personality trait of absorption exhibit greater physiological stress reactivity.