bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Year Incidence of Hyperosmolar States and Prognosis in a Geriatric Acute Care Unit
Authors: Bourdel-Marchasson Isabelle , Proux Sebastien , Dehail Patrick , Muller François , Richard-Harston Sandrine , Traissac Thalie , Rainfray Muriel
Published: May 2004

Background: Hyperosmolar syndromes are associated with high mortality rates, yet little is known about their incidence and their prognosis. Objective: To determine the 1-year incidence of hyperosmolar states and the prognostic factors for in-hospital and 1-year mortality. Method: A 6-month prospective cohort study was conducted in a 40-bed acute care geriatric unit and included all patients who developed plasma osmolarity of 320 mosm/l or greater. Age, sex and known cognitive impairment as possible risk factors of hyperosmolarity were assessed. In-hospital and 1-year mortality were calculated and risk factors for death among baseline patient characteristics were sought. Results: 48 (11) of the 436 inpatients in the study were identified as hyperosmolar. Diabetic hyperosmolarity was found in 8 patients. Cognitive impairment was a risk factor for hyperosmolarity (relative risk 2.39, 95% confidence interval 2.18–3.33, p < 0.001), but not age or sex. Infections were accompanied by hyperosmolarity in 30 (62.5). Thirty-five patients (72.9) were bed- or chair-ridden. In-hospital mortality was higher in hyperosmolar patients (35.4) than in the others (16.7%, p = 0.003). Causes of death were infection in 5 (29.4), terminal cachexia in 5, thrombosis in 3, gastric bleeding in 1, renal failure in 2 and heart failure in 1. Functional dependency for mobility was a risk factor for in-hospital mortality but not the degree of hyperosmolarity. One-year mortality was 68.7%. Functional dependency and pressure ulcers were independent predictors of 1-year mortality (p = 0.005 and p = 0.044, respectively). Conclusion: Hyperosmolar states occurred in cognitively impaired and dependent patients and resulted in high mortality rates at short and at mid-term. Mortality was related to functional dependency rather than to hyperosmolarity.
Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs
Authors: Boskabady M.H. , Zarei A.
Published: May 2004

Despite the controversy of bronchial responsiveness to β2-agonist drugs in asthma, in a previous study we have shown increased responsiveness of asthmatic tracheobronchial tree to isoprenaline. Therefore, in the present study, tracheal responsiveness to isoprenaline and also β-adrenergic receptor blockade were studied in sensitized guinea pigs. An experimental model of asthma was induced in guinea pigs by sensitization of animals with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of sensitized and control animals to cumulative concentrations of isoprenaline (I) in the absence and presence of 10 nmol/l propranolol were measured, and the effective concentration of I causing 50% of maximum response (EC50 I) was obtained. The propranolol blockade (CR – 1) was calculated by: (post-propranolol EC50 I/EC50 I) – 1. Tracheal responses of sensitized and control animals to cumulative concentrations of methacholine (M) were also measured and EC50 M were obtained. The tracheal responses of sensitized guinea pig to isoprenaline was significantly higher than that of the control animals (EC50 I for sensitized and control animals were 0.24 ± 0.04 and 0.58 ± 0.07 µmol/l, respectively; p < 0.001).The β-adrenergic receptor blockade by propranolol (CR – 1) was also significantly higher in sensitized guinea pigs than that of the control animals (p < 0.001). The results of this study indicate an increased tracheal response to β-adrenergic-stimulating drug and enhancement of β-adrenergic blockade by propranolol in the sensitized guinea pig.
Mechanism of Heme Oxygenase-1 Gene Induction by Quercetin in Rat Aortic Smooth Muscle Cells
Authors: Lin Hui-Chen , Cheng Tzu-Hurng , Chen Yen-Chou , Juan Shu-Hui
Published: May 2004

We previously reported that adenovirus-mediated gene transfer of heme oxygenase-1 (HO-1) inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. This finding implies that HO-1 induction is beneficial for protecting blood vessels. We also found that quercetin, a common polyphenolic compound in foods of plant origin, induces HO-1 expression in RAW264.7 cells. This study was aimed at examining the potency of quercetin as a HO-1 inducer and its regulation in rat aortic smooth muscle cells (RASMCs). We showed that quercetin-induced HO-1 production was in time- and dose-dependent fashions, and that this regulation occurred at both transcription and translation levels. Quercetin increased p38 mitogen-activated protein kinase (p38MAPK), but inhibited extracellular signal-regulated kinase in RASMCs. The level of quercetin-induced HO-1 expression was attenuated by SB202190 (a p38MAPK inhibitor). Taken together from the data in this study, we suggest that quercetin induced HO-1 expression, at least in part, through p38MAPK.
Macro- and Microanatomical Characterization of the Cat Brachial Plexus
Authors: Aubert L. , Carozzo C. , Devillaire A-C. , Crevier-Denoix N. , Moissonnier P.
Published: May 2004

The anatomy of the cat brachial plexus is poorly documented despite its importance for reparative surgery. The present work aims to study the anatomy of the brachial plexus of 20 European cats and to analyze the radicular constituents of 10 of them using histological techniques. The plexus radicular constitution is very homogeneous and is mainly composed of the ventral rami (also called ventral branches) arising from C6, C7, C8 and T1 spinal nerves. The fascicular and axonal structure is more variable. C8 is the ventral ramus that contains the largest number of axons (16,673 ± 3,307), and is composed of 6.7 ± 3.5 fascicles. The radial nerve is the peripheral nerve that contains the largest number of axons (11,245 ± 2,217), and is composed of 7.3 ± 3.8 fascicles. The number of nervous fibers does not differ proportionally to the weight of the cat, or between the right or the left side. Our data could help neurotization and entubulation repair after brachial plexus injury.
Systematic Overview of the Pharmacological Management of Postherpetic Neuralgia
Authors: Plaghki L. , Adriaensen H. , Morlion B. , Lossignol D. , Devulder J.
Published: May 2004

Objective: This study systematically reviews current evidence on drug treatments commonly used in postherpetic neuralgia. Methods: Randomized controlled trials were critically selected using predefined search criteria. Efficacy was evaluated as percentage of improvement in pain intensity between baseline and endpoint, tolerability by number of study discontinuations because of adverse events and incidence of adverse events. Results: Currently published trials enrolled different patient populations and small patient numbers. The great variability in doses, titration schemes, designs and washout periods together with other design flaws made comparison between different studies scientifically impossible. Conclusions: There is a real need for well-performed clinical trials with standardization in design and reporting. Development of adequate and validated questionnaires for evaluation and comparison of efficacy and safety of treatments is also needed. Based on the evaluation of individual studies, it is concluded that only gabapentin is studied in large (over 200 patients), placebo-controlled studies showing good efficacy and safety.
Use of Duplex Ultrasonography in the Treatment of Thromboangiitis obliterans with Iloprost
Authors: Noël B. , Panizzon R.G.
Published: May 2004

We present a 34-year-old patient with digital necrosis due to thromboangiitis obliterans. He was successfully treated with iloprost, a prostaglandin analogue. Duplex ultrasonography was performed during the perfusion of iloprost to optimize the doses and the treatment duration. A complete revascularization was observed after 10 days. Iloprost perfusions were stopped, and a slow regression of the necroses was observed in the subsequent days. With the use of duplex ultrasonography, unnecessary high doses of iloprost and long periods of treatment can be avoided reducing side effects and treatment costs.
First Report of Arthroderma benhamiae in Switzerland
Authors: Fumeaux Janine , Mock Myriam , Ninet Béatrice , Jan Isabelle , Bontems Olympia , Léchenne Barbara , Lew Daniel , Panizzon Renato G. , Jousson Olivier , Monod Michel
Published: May 2004

Background: Dermatophytes are usually identified on the basis of macroscopic characteristics and microscopic examination of the cultures. Identification of dermatophytes often remains difficult or uncertain because there are variations from one isolate to another and overlapping characteristics between species. Objective: To identify dermatophyte species producing numerous microconidia and resembling Trichophyton mentagrophytes by DNA sequence analysis. Methods: The complete ITS1 + 5.6s + ITS2 rDNA region of various dermatophytes isolated in culture was amplified by PCR and sequenced. Results: Nine isolates of a fast-growing dermatophyte species were identified as Arthroderma benhamiae by DNA sequencing. Retrospective investigations revealed that the isolates were from 8 children and 1 adult suffering from inflammatory dermatophytosis. Eight of the 9 patients had had previous contact with rodents, mostly guinea pigs. Conclusion: It is the first time that A. benhamiae is reported in Switzerland. In cases of dermatophytosis attributed to A. benhamiae, a rodent is the most likely cause of infection.
Micronodular Kaposi’s Sarcoma – A New Variant of Classic-Sporadic Kaposi’s Sarcoma
Authors: Kempf Werner , Cathomas Gieri , Burg Günter , Trüeb Ralph M.
Published: May 2004

Kaposi’s sarcoma (KS) in its classic-sporadic form is a rare vascular neoplasm affecting predominantly elderly men of Jewish or Mediterranean origin. Women are very rarely affected by KS. The tumor manifests itself most commonly with brownish macular or infiltrated oval lesions on the lower legs in both genders. Human herpesvirus 8 (HHV-8) has recently been demonstrated to be etiologically linked to KS. We report a 51-year-old HIV-seronegative Caucasian woman with an unusual, previously not described variant of KS which presented with small (3 mm in diameter) scattered firm red papules on her right arm. The histology with nodular spindle cell tumor expressing endothelial markers, the demonstration of serum antibodies against HHV-8 and the presence of viral nucleic acids in the lesional tissue proved the diagnosis of the nodular stage of KS. An indolent course characterized by clinically identical seasonal recurrences, even after surgical treatment and cryosurgery, was observed during the follow-up period of 9 years. We propose the term ‘micronodular KS’ for this unusual clinical variant of KS mimicking capillary hemangioma.
Purpura fulminans in a Child as a Complication of Chickenpox Infection
Authors: Campanelli Alexandre , Kaya Gürkan , Ozsahin Ayse Hulya , La Scala Giorgio , Jacquier Cédric , Stauffer Mélanie , Boehlen Françoise , de Moerloose Philippe , Saurat Jean-Hilaire
Published: May 2004

Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very low protein S levels as well as anticardiolipin antibodies. Aggressive treatment by low-molecular-weight heparin, steroids, intravenous immunoglobulins and fresh frozen plasma was able to prevent the extension of the lesions and to correct the coagulation abnormalities. No lesions required skin grafting. As in our patient, an acquired protein S deficiency is probably responsible for most cases of purpura fulminans occurring after varicella, but the concomitant presence of antiphospholipid antibodies may also play a role.
Cutaneous Myiasis due to Dermatobia hominis
Authors: Hohenstein E.J. , Buechner S.A.
Published: May 2004

Cutaneous myiasis caused by the human botfly Dermatobia hominis involves the infestation of tissue with dipterous fly larvae and is common in the neotropical region of the New World. We report a case of D. hominis imported in Switzerland from Costa Rica. In the past, various approaches to extract the botfly larva have been reported.
Association between Norepinephrine Transporter Gene Polymorphism and Major Depression
Authors: Ryu Seung-Ho , Lee Seung-Hwan , Lee Heon-Jeong , Cha Ji-Hyun , Ham Byung-Joo , Han Chang-Su , Choi Myoung-Jin , Lee Min-Soo
Published: May 2004

Noradrenergic and serotonergic abnormalities have long been implicated in patients with major depression. The novel selective norepinephrine reuptake inhibitor reboxetine has been shown to be at least as effective as imipramine, desipramine and fluoxetine in the treatment of major depression. It is suggested that the dysfunction of the norepinephrine transporter (NET) may be related to major depression. Although the transcriptional activity related to the NET gene expression is little known, it may be a good candidate gene for major depression. Therefore, we investigated whether the T-182C polymorphism of the NET gene is associated with major depression in a Korean sample of 112 major depression patients compared with 136 healthy controls. We found a significantly lower frequency in TT genotype in patients with major depression than in normal controls when the genotypes of T-182C polymorphism were classified into two groups: TT group versus TC + CC group (p = 0.019). This result suggests that the T-182C polymorphism in the NET gene might be associated with major depression.
Quetiapine Treatment for Behavioral and Psychological Symptoms in Patients with Senile Dementia of Alzheimer Type
Authors: Fujikawa Tokumi , Takahashi Terumichi , Kinoshita Akiko , Kajiyama Hiroaki , Kurata Akiko , Yamashita Hidehisa , Yamawaki Shigeto
Published: May 2004

The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25– 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles.
Renal Disease as a Predictor of Increased Mortality among Patients with Rheumatoid Arthritis
Authors: Sihvonen S. , Korpela M. , Mustonen J. , Laippala P. , Pasternack A.
Published: May 2004

Aims and Methods: Mortality among RA patients and controls was analyzed with special attention to renal disease in population-based material (originally screened in 1988) of 604 patients with RA (470 females, 134 males) and 457 age- and sex-matched controls (352 females, 105 males). In the original RA population, isolated hematuria (HU) was observed in 54, isolated proteinuria (PU) in 27, combined hematuria and proteinuria (HUPU) in 7, chronic renal failure (CRFtot) in 36 and isolated chronic renal failure without HU or PU (CRFisol) in 15 patients. Among the controls, HU was observed in 39, PU in 11, CRFtot in 32 and CRFisol in 16 subjects. HUPU was not observed in any of the controls. Microalbuminuria (20–200 µg/min) was observed in 34 RA patients and in 27 controls. Histologically confirmed amyloidosis was found in 13 RA patients and mesangial glomerulonephritis (MesGN) in 17 patients. The mortality was evaluated in 1999 from data of the Statistical Office of Finland. Statistical analysis was performed by Cox regression analysis. Results: Mortality was significantly increased in the RA population as compared to controls: hazard ratio (HR) 1.78 (95% CI 1.34–2.31) for all RA patients; HR 2.12 (1.52–2.94) for females; HR 1.15 (0.75–1.77) for males. In the RA material, increased mortality was detected in patients with HUPU (HR 4.45; 1.54–12.84), PU (HR 3.54; 1.88–6.65), CRFtot (HR 3.74; 2.55–5.56) or microalbuminuria (HR 2.77; 1.64–4.69) when compared to those with normal clinical renal findings, whereas HU (HR 1.49; 0.88–2.52), CRFisol (HR 1.71; 0.82–3.54), bacteriuria (HR 0.96; 0.35–2.59) or pyuria (HR 0.65; 0.09–4.65) did not predict mortality. Renal amyloidosis was associated with an over twofold mortality rate (HR 2.31; 1.03–5.15), whereas mortality was within expected limits in RA patients with MesGN (HR 1.61; 0.49–5.24). Conclusion: Our results show that nephropathy presenting with combined hematuria and proteinuria, proteinuria, microalbuminuria or histologically confirmed amyloidosis is associated with increased mortality in RA patients, whereas mortality is within expected limits in those with isolated hematuria or mesangial glomerulonephritis.
Association of FMF-Related (MEFV) Point Mutations with Secondary and FMF Amyloidosis
Authors: Atagunduz M. Pamir , Tuglular Serhan , Kantarci Gulcin , Akoglu Emel , Direskeneli Haner
Published: May 2004

Background: Familial Mediterranean fever (FMF) is the major cause of AA amyloidosis in Turkey. M694V mutation in MEFV gene was suggested to be associated with severe clinical features and amyloidosis of FMF. Methods: In this study, the frequencies of three FMF-related MEFV mutations (M694V, M680I and V726A) were investigated in FMF patients with (AA-FMF, n = 37) and without amyloidosis (non-AA-FMF, n = 35), in patients with secondary amyloidosis related to non-FMF inflammatory conditions (S-AA, n = 19) and in a non-inflammatory control group (n = 185) by molecular genetic studies using polymerase chain reaction with the ARMS (amplification refractory mutation system) method. Results: Both AA and non-AA-FMF patients had significantly higher MEFV mutations compared to non-inflammatory controls (81 and 62.7% respectively vs. 4.2%, p = 0.0001). AA-FMF patients carried significantly more MEFV mutations than non-AA-FMF patients (p = 0.01). M694V was the most common mutation in both FMF groups (63.5 vs. 51.4%), however allele frequency (p = 0.17) and the number of homoyzgous patients for this mutation did not differ between the groups (p = 0.77). Although lower compared to FMF patients, S-AA patients also had a significantly higher incidence of MEFV mutations than non-inflammatory controls (21 vs. 4.2%) (p = 0.0002). M694V was the only MEFV mutation in this group. Conclusion: MEFV mutations are found to be increased both in FMF and non-FMF associated secondary amyloidosis in our study; however, no clear association between M694V and amyloidosis is observed, except in the non-FMF group. Our results suggest that MEVF mutations may also serve as a severity marker for other inflammatory conditions.
Accelerated Glomerular Injury in Hemi-Nephrectomized Transgenic Mice of Mesangial Cell-Predominant Serpin, Megsin
Authors: Onogi Hiroshi , Inagi Reiko , Nangaku Masaomi , Ueda Yasuhiko , Miyata Toshio , Kurokawa Kiyoshi
Published: May 2004

Mesangial cells play a critical role in the maintenance of normal glomerular functions such as matrix remodeling and immune complex disposal. We recently identified a novel human mesangium-predominant gene, megsin, which is a new member of the serine protease inhibitor (serpin) superfamily. While our previous studies demonstrated progressive mesangial matrix expansion and an increase in the number of mesangial cells in megsin transgenic mice, it took 40 weeks to develop these manifestations. Here we performed hemi-nephrectomy to accelerate glomerular injury in megsin transgenic mice. Hemi-nephrectomized transgenic mice developed focal segmental mesangial expansion, which was associated with proteinuria. Megsin has thus a biologically relevant influence on the development of glomerular damage. The hemi-nephrectomized model of this transgenic mouse might serve as a tool to investigate the mechanisms of glomerular disease.
Chlamydia pneumoniae and Atherosclerosis: No Way-Out or Long Way?
Authors: Tsirpanlis George
Published: May 2004

Recently, Chlamydia pneumoniae is the microorganism frequently implicated in the infection-based inflammatory atherogenous hypothesis. Although in vitro experimental data and initial sero-epidemiologic, pathology-based studies and antibiotic trials supported this interesting hypothesis, later data are conflicting. Some confounding factors are the causes of uncertainty; lacking of standard methods for C. pneumoniae detection, co-existence of other atherosclerotic risk factors and anti-inflammatory effects of antibiotics used in clinical trials seem to be the principal ones. Standardization of methodology used, antibiotic trials with a different orientation-design and a vaccine preparation that eventually will be tested in clinical trials with a long follow-up, should provide a definite answer regarding the probability C. pneumoniae to be a main, a secondary or an irrelevant factor to atherosclerosis. Studies linking C. pneumoniae to inflammation and accelerated atherosclerosis in renal failure patients are accumulated but limitations are similar to the above mentioned.
Pulse Pressure and Left Ventricular Diastolic Dysfunction in Hypertensive Patients
Authors: Trika Chrysanthi O. , Zakopoulos Nikolaos , Toumanidis Savvas T. , Stamatelopoulos Stamatios F. , Moulopoulos Spyridon D.
Published: May 2004

Background: Impaired left ventricular diastolic function is a common finding in essential hypertension. Methods: In order to investigate possible relationships between flow velocity through the mitral valve (E/A; index of left ventricular diastolic function) and 24-hour blood pressure and heart rate variations, 198 patients with mild to moderate essential hypertension were studied by Doppler echocardiography and ambulatory blood pressure monitoring. They were divided according to age into group 1 (n = 88, age 40–54 years) and group 2 (n = 110, age 55–79 years). Each group was divided into subgroups with (1a, 2a) or without (1b, 2b) left ventricular hypertrophy according to the end-diastolic posterior wall thickness and/or the interventricular septum thickness. Results: In a multivariate stepwise regression analysis, age (β = –0.25, p < 0.0001), posterior wall thickness (β = –0.31, p < 0.0057) and mean heart rate during the day (β = –0.34, p < 0.0284) were the independent predictors of E/A in the pooled population. In group 1a (young subjects with left ventricular hypertrophy), mean systolic blood pressure during the night (β = –0.33, p < 0.041) was the only independent predictor of E/A. In the elderly group without left ventricular hypertrophy (group 2b), the mean heart rate during the day (β = –0.44, p < 0.0000) and mean pulse pressure during the night (β = –0.60, p < 0.0007) were the independent predictors of E/A. Conclusions: The new finding provided by this study is that in elderly hypertensive patients without left ventricular hypertrophy, a large pulse pressure at night may serve as an independent predictor of abnormal left ventricular diastolic filling.
Contribution of Glutamine Synthetase to Ammonia-Induced Apoptosis in Gastric Mucosal Cells
Authors: Kubota Yuuji , Kato Katsuaki , Dairaku Naohiro , Koike Tomoyuki , Iijima Katsunori , Imatani Akira , Sekine Hitoshi , Ohara Shuichi , Matsui Hiroshi , Shimosegawa Tooru
Published: May 2004

Background/Aims: Glutamine synthetase is a key enzyme necessary for ammonia detoxification in the brain, but excessive activation of this enzyme can be cytotoxic to neural cells as a consequence of excessive consumption of ATP and glutamate. The stomach also expresses high levels of glutamine synthetase and this study aimed to investigate a possible pathophysiological role of glutamine synthetase in ammonia-induced gastric mucosal injury. Methods: Normal rat gastric mucosal epithelial (RGM-1) cells were treated with ammonia, and a specific glutamine synthetase inhibitor (methionine sulfoximine) was used to assess the action of glutamine synthetase. Results: Treatment with ammonia induced apoptotic cell death. Increased expression of p21 and Bax, decreased expression of Bcl-2, cytochrome C release from the mitochondria into the cytosol and subsequent activation of caspase-9 and -3 were identified in the cells treated with ammonia, although there was no apparent change in p53 expression. On the other hand, pretreatment with various concentrations of methionine sulfoximine reduced the glutamine synthetase activity in ammonia-treated RGM-1 cells, and prevented the induction of apoptosis and the reduction in intracellular ATP levels in a dose-dependent manner. Conclusions: Our results suggested that the energy exhaustion which resulted from an overload of ammonia to glutamine synthetase may have initiated the apoptotic signaling in gastric mucosal cells.
Individualized Risk Management in Diabetics: How to Implement Best Practice Guidelines – Design and Concept of the IRIDIEM Studies
Authors: Lameire N. , Stevens P. , Raptis S. , Thomas S. , Schernthaner G.
Published: May 2004

The prevalence of type 2 diabetes mellitus is rising rapidly in all developed countries, particularly in the growing population of persons >50 years of age. As a dangerous consequence, this is accompanied by a proportionate increase in the incidence of chronic renal disease. Evidence-based medicine has shown that tight blood glucose control can delay the onset and retard the progression of diabetic complications, and while it is a challenge to closely manage the complexity of diabetes, it is more difficult to effectively treat the multiple associated comorbidities that develop. Best practice guidelines support early intervention and aggressive treatment of hypertension, hyperglycaemia, proteinuria, hypercholesterolemia, and anaemia. To date, guideline-based management has been proven to be difficult. This article describes the concept of the IRIDIEM studies. The objective of these studies is to endorse and facilitate the use of current best practice guidelines for the management of frequent comorbid diseases and established risk factors in the treatment of type 2 diabetes associated with chronic kidney disease. Additionally, IRIDIEM will assess the impact of this improved disease management model on the progression of chronic kidney disease that can result from electronically prompting clinicians with evidence-based treatment advice.
Protein Methylation Activates Reconstituted Ryanodine Receptor-Ca2+ Release Channels from Coronary Artery Myocytes
Authors: Chen Ya-Fei , Zhang Andrew Y. , Zou Ai-Ping , Campbell William B. , Li Pin-Lan
Published: May 2004

Ryanodine receptors (RyR) play an important role in the regulation of intracellular Ca2+ concentration and in the control of vascular tone. However, the mechanism regulating the activity of RyR is poorly understood. The present study determined whether protein methylation participates in the control of RyR activity. Using a planar lipid bilayer clamping system, S-adenosyl-L-methionine (SAM), a methyl donor, significantly increased the activity of a 245-pS reconstituted Ca2+ release channel from coronary arterial smooth muscle (CASM) in a concentration-dependent manner. Addition of the protein methylation blockers, 3-deazaadenosine, S-adenosylhomocysteine or sinefungin into the cis solution markedly attenuated SAM-induced activation of RyR/Ca2+ release channels. By Western blot analysis, arginine N-methyltransferase (PRMT1) and FK506 binding protein (FKBP) were detected in the SR used for reconstitution of RyR. In the presence of anti-PRMT1 antibody (1:100), SAM-induced activation of RyR/Ca2+ channel was completely abolished. In addition, this SAM-induced increase in RyR/Ca2+ channel activity was blocked by 30 µM ryanodine and by FK506 (100 µM), a ligand for the RyR accessory protein. These results suggest that protein methylation activates RyR/Ca2+ release channels and may participate in the control of intracellular Ca2+ mobilization in CASM cells by transferring a methyl group to the arginine moiety of the RyR accessory protein, FKBP 12.
Technologies in the Evaluation of Irritable Bowel Syndrome
Authors: Smout A.J.P.M. , Azpiroz F. , Brummer R.-J. , Coremans G. , Dapoigny M. , Müller-Lissner S.A. , Pace F. , Stockbrügger R.W. , Vatn M. , Whorwell P.J.
Published: May 2004

During a meeting in The Hague, The Netherlands, the IBiS Club evaluated the most important techniques that can be used in the investigation of irritable bowel syndrome, either in the context of scientific research or as a clinical diagnostic tool. In each of these, the relevance of findings made in irritable bowel syndrome was balanced against the applicability of the technique. The discussion of the group is summarized in this paper.
Extended Microsatellite Analysis in Microsatellite Stable, MSH2 and MLH1 Mutation-Negative HNPCC Patients: Genetic Reclassification and Correlation with Clinical Features
Authors: Schiemann U. , Müller-Koch Y. , Gross M. , Daum J. , Lohse P. , Baretton G. , Muders M. , Mussack T. , Kopp R. , Holinski-Feder E.
Published: May 2004

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. Aim of the Study: The study cohort consisted of 25 HNPCC index patients (19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS) – or low instable (MSI-L) – tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. Results: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H (high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 ± 4.9 years (vs. 47.0 ± 14.6 and 49.8 ± 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped (78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. Conclusion: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC.
Hypoplasia of the Parabrachial/Kölliker-Fuse Complex in Perinatal Death
Authors: Lavezzi Anna Maria , Ottaviani Giulia , Rossi Lino , Matturri Luigi
Published: May 2004

We report the first observation of perinatal death attributable to morphological alterations of the parabrachial/Kölliker-Fuse complex. In an infant, born at 41 weeks of gestation with severe signs of asphyxia and dead 20 h after delivery, we observed the presence of rare and immature neurons in the brain stem areas of both lateral and medial parabrachial nuclei and the absence of the characteristic neurons of the Kölliker-Fuse nucleus. Such hypoplasia was associated with severe hypoplasia of the arcuate nucleus and pulmonary hypoplasia.
Transferrin Microheterogeneity in Fetal Blood
Authors: Wu Y. , Sakamoto H. , Kanenishi K. , Tanaka S. , Ueno M. , Hata T.
Published: May 2004

Objectives: To investigate the distribution of microheterogeneous subfractions of transferrin in fetal blood and the influence of highly sialylated transferrins on fetal growth. Study Method: Serum transferrin concentrations were determined by a standard turbidimetric assay. Microheterogeneous transferrin subfractions were assessed by crossed immunoisoelectric focusing. Results: In normal term infants, total serum transferrin concentrations and percent distribution of highly sialylated transferrins (≧5-sialo-transferrins) were markedly lower; the percent distributions of hyposialylated transferrins (0- and 1-sialo-transferrins) were apparently higher than those in non-pregnant and pregnant women. There was no significant positive correlation between the serum concentrations of total transferrin or highly sialylated transferrins in infants’ blood and birth weights (r = 0.187, p = 0.582; r = 0.374, p = 0.257, respectively). Conclusion: The transferrin microheterogeneity pattern shifted towards reduced glycosylation and sialylation in addition to a decrease in total transferrin concentration in fetal blood compared to that of non-pregnant and pregnant women. The concentrations of serum total transferrin and the highly sialylated transferrins in fetal blood, if higher than a certain level, did not seem to have any influence on normal fetal growth.
Rapid D-dimer test combined a clinical model for deep vein thrombosis
Authors: Friera Alfonsa , Artieda Pilar , Caballero Paloma , Moliní Pilar , Morales Marta , Suárez Carmen , Ruiz-Giménez Nuria ,   Thromboembolic Disease Group4
Published: May 2004

An optimal approach to the diagnosis of deep vein thrombosis (DVT) in lower limbs in the emergency department is still unknown. In this prospective cohort study, we aimed to evaluate the accuracy of the widely available plasma D-dimer test (VIDAS) and establish the usefulness of combining D-dimer testing with a clinical model to reduce the need for serial ultrasonographies and improve the diagnostic strategy of DVT. We performed a cohort study in 383 consecutive outpatients referred to the emergency department of Hospital La Princesa, with clinical suspicion of DVT. The patients were stratified into three pre-test probability categories using an explicit clinical model (Wells score), and underwent a quantitative automated ELISA D-dimer assay (VIDAS D-Dimer® bioMérieux). Patients were managed according to the diagnostic strategy based on clinical probability and compression ultrasonography (CU). Patients for whom DVT was considered a high pre-test probability with negative ultrasonographic findings in the initial CU, returned the following week for repeat ultrasonography. All patients with DVT excluded did not receive anticoagulant therapy, and were followed up for three months to monitor the development of venous thromboembolic complications. DVT was confirmed in 102 patients (26.6%): 95 in the initial test, four in the second test, and three who developed venous thromboembolic complications in the three-month follow-up period. The calculated D-dimer cut-off level was 1 µg/ml. One hundred patients (98%) with DVT had positive D-dimer. D-dimer had a sensitivity of 98% and a negative predictive value of 98.6%. Among the high-probability patients with positive D-dimer tests and initial negative CU, 9.75% had DVT on repeat CU at one week. The study results suggest that the addition of VIDAS D-dimer to this diagnostic algorithm could improve the management of patients with suspected DVT in daily practice. A diagnostic approach of DVT based on D-dimer (cut-off ≥1 μg/ml) as the first diagnostic tool for the exclusion of DVT, and the clinical probability model as the tool that identifies those patients requiring a second ultrasonography is useful and suitable for daily medical practice.
P-cresol, a uremic retention solute, alters the endothelial barrier function in vitro
Authors: Dou Laetitia , Anfosso Francine , Sabatier Florence , Moal Valérie , Glorieux Griet , De Smet Rita , Vanholder Raymond , Dignat-George Françoise , Sampol José , Berland Yvon , Brunet Philippe , Cerini Claire
Published: May 2004

Patients with chronic renal failure (CRF) exhibit endothelial dysfunction, which may involve uremic retention solutes that accumulate in blood and tissues. In this study, we investigated the in vitro effect of the uremic retention solute p-cresol on the barrier function of endothelial cells (HUVEC). P-cresol was tested at concentrations found in CRF patients, and since p-cresol is protein-bound, experiments were performed with and without physiological concentration of human albumin (4 g/dl).With albumin, we showed that p-cresol caused a strong increase in endothelial permeability after a 24-hour exposure. Concomitant with this increase in endothelial permeability, p-cresol induced a reorganization of the actin cytoskeleton and an alteration of adherens junctions. These molecular events were demonstrated by the decreased staining of cortical actin, associated with the formation of stress fibers across the cell, and by the decreased staining of junctional VE-cadherin. This decrease in junctional VE-cadherin staining was not associated with a reduction of membrane expression. Without albumin, the effects of p-cresol were more pronounced. The specific Rho kinase inhibitor, Y-27632, inhibited the effects of p-cresol, indicating that p-cresol mediates the increase in endothelial permeability in a Rho kinase-dependent way. In conclusion, these results show that p-cresol causes a severe dysfunction of endothelial barrier function in vitro and suggest this uremic retention solute may participate in the endothelium dysfunction observed in CRF patients.
Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels
Authors: Marcucci Rossella , Fatini Cinzia , Gensini Francesca , Sticchi Elena , Sodi Andrea , Cappelli Stefania , Menchini Ugo , Gensini Gian , Abbate Rosanna , Prisco Domenico , Gori Anna
Published: May 2004

Few and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18–83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20–84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95th percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70–14.30; p = 0.003).The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.013.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89–12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hypertension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.1857.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.
Apoptotic-like mitochondrial events associated to phosphatidylserine exposure in blood platelets induced by local anaesthetics
Authors: Augereau Olivier , Rossignol Rodrigue , DeGiorgi Francesca , Mazat Jean-Pierre , Letellier Thierry , Dachary-Prigent Jeanne
Published: May 2004

Phosphatidylserine exposure in platelets is required for normal haemostasis and is also a hallmark of apoptosis. It results from activation of a phospholipid scramblase, which has been shown to be differently stimulated by Ca2+-influx and during apoptosis, thus suggesting that mitochondria may be involved in phosphatidylserine exposure in platelets. It is also well known that local anaesthetics can expose phosphatidylserine in platelets and affect the mitochondrial metabolism in other cells. Thus, the present study was undertaken to evaluate the specific involvement of mitochondria in phosphatidylserine exposure in platelets. For this purpose, we stimulated phosphatidylserine exposure by local anaesthetics and avoided any external Ca2+-influx by performing all experiments in the absence of added Ca2+. We report that phosphatidylserine exposure, induced by the lipophilic local anaesthetics dibucaine and tetracaine, was accompanied by depolarization of the mitochondrial membrane, cytochrome c release, calpain-processing of caspases 9 and 3 to active enzymes, as well as a prolonged increase in both cytosolic and mitochondrial Ca2+ concentrations. In contrast, in the absence of extracellular Ca2+, the Ca2+-ionophore A23187 induced a smaller transient increase in both cytosolic and mitochondrial Ca2+ concentrations, but did not induce any other phenomena, nor phosphatidylserine exposure. However, phosphatidylserine exposure and depolarization induced by dibucaine still occurred in spite of inhibition of intracellular Ca2+ elevation. Thus we conclude that phosphatidylserine exposure in platelets is associated with mitochondrial apoptotic-like events. Therefore, we propose that mitochondria engagement in an apoptotic pathway in platelets could lead to PS exposure without the participation of Ca2+.
Coagulation activation in young survivors of myocardial infarction (MI) - a population-based case-control study
Authors: Børvik Trond , Sandset Per , Bønaa Kaare , Nordøy Arne , Hansen John-Bjarne , Brodin Ellen
Published: May 2004

Formation of an occlusive thrombus by exposure of tissue factor (TF) to circulating blood and subsequent triggering of coagulation by TF-FVIIa complexes on ruptured atherosclerotic plaques is thought to be a key event in acute MI. Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation by neutralizing FXa and inhibiting the TF-FVIIa complex. A case control study was conducted to investigate the role of coagulation activation in MI. Sixty-two patients with verified MI, 40-60 yrs of age, were recruited into the study and examined 1-4 years after the acute coronary event. Thrombinantithrombin complex (TAT) was significantly increased in MI patients (8.2 ± 12.9 µg/l vs. 3.9 ± 2.6 µg/l, p=0.01). In contrast, FVIIa was lower in MI patients (41 ± 13 mU/ml vs. 48 ± 15 mU/ml, p=0.003) accompanied by an increase in plasma free TFPI antigen (20.9 ± 5.0 ng/ml vs. 19.2 ± 4.9 ng/ml, p=0.03). Significant trends for increase in triglycerides and total cholesterol across quartiles of free TFPI Ag were found in both groups, whereas HDL cholesterol decreased across quartiles of TFPI among control subjects. The compensatory increase in plasma free TFPI with established lipid and haemostatic risk factors were abrogated in the MI patients. An apparent increase in the basal activation of the coagulation system was observed in young patients with MI. Enhanced coagulation activation was accompanied by a decrease in FVIIa and increase in free TFPI Ag, probably reflecting a modest triggering of TF-induced coagulation in these patients.
Admission troponin T, advanced age and male gender identify patients with improved myocardial tissue perfusion after abciximab administration for ST-segment elevation myocardial infarction
Authors: Lehrke Stephanie , Katus Hugo , Giannitsis Evangelos
Published: May 2004

The aim was to investigate the effect of abciximab on microvascular perfusion in different subgroups of patients undergoing direct PCI for acute STEMI. We enrolled 145 consecutive patients with TIMI grade 3 flow after direct PCI for acute STEMI. The GPIIb/IIIa inhibitor abciximab was administered in 57 patients (39.3%). Myocardial perfusion was the primary outcome measure and was assessed by analysis of cardiac troponin T wash-out. Treatment effects on myocardial perfusion and clinical outcome were tested for predefined subgroups including patients with an admission cTnT > 0.1µg/L, diabetes mellitus, male gender, age > 70 years, and time from symptom onset to reperfusion > 6 hours. A significant improvement of cTnT washout was seen in patients with an admission cTnT ≥ 0.1 µg/L, in males and in older patients. Improved tissue level reperfusion did not translate into a significant reduction of cardiac mortality or the incidence of the combined endpoint consisting of cardiac death, nonfatal reinfarction and need for target vessel revascularisation during 30 dayand long-term follow-up (mean 274 days). In conclusion, adjunctive administration of abciximab improves myocardial perfusion in patients with normal epicardial flow after direct PCI, particularly in patients with an cTnT > 0.1µg/L on admission, age over 70 years and male gender.