Biomedical subjects

M Zeller

Publications and source records attributed to M Zeller.

At least 37 records · Page 2Linked to original sources

PubMed2003

[Factor V Leiden and myocardial infarction: a case, review of the literature with a meta-analysis].

Mutation in blood coagulation factor V Leiden is the most frequently genetic polymorphism implied in venous thrombosis. A 57 year old man was hospitalised for acute myocardial infarction (MI). An emergency coronary angiography was performed, and no significant stenosis was observed. The haematologic check-up showed an heterozygous Leiden mutation of factor V. We report all publications about the relation between factor V Leiden and coronary thrombosis, and we performed a meta-analysis. We analysed the relation in general population and in subgroups, such as, younger and older, and patient with or without coronary stenosis. In global population, the meta-analysis did not found significant association between Factor V Leiden and myocardial infarction (OR = 1.25; IC = 0.97-1.58). In contrast, in patients less than < 55 years old after MI, Factor V Leiden prevalence was significantly higher than in control group (OR = 1.48; IC = 1.05-2.08). In addition, after MI without significant coronary stenosis Factor V Leiden prevalence was significantly higher than in normal patients (OR = 2.84; IC = 1.46-5.51). After MI, in patients without significant coronary stenosis, Factor V Leiden prevalence was significantly higher than in patients with significant coronary stenosis (OR = 3.26; IC = 1.67-6.36). Our study suggests that Factor V Leiden could be search after MI in young subjects and/or without significant stenosis.

Activated Protein C Resistance↗

PubMed2003

Intramural neovascularization and haemorrhages are major long-term effects of intravascular gamma-radiation after stenting.

Structural changes that might influence the structural integrity of the vessel in response to intravascular brachytherapy (IVB) and stenting were examined, focus being on the importance of neovascularization in rabbit stented arteries. Stents were implanted in the infrarenal aortas of rabbits, immediately followed by gamma IVB or a sham radiation procedure, and the arteries harvested at 6 months. Labelling for von Willebrand factor showed an increase in adventitial and medial neovascularization in irradiated versus control arteries group (5.04+/-0.89 versus 1.51+/-0.23 mm(-2), respectively; p=0.004). Moreover, intramedial haemorrhages (free hemosiderin deposition) and inflammation (macrophages) were only observed in irradiated arteries. No significant change in expression of matrix metalloproteinase 1, 2 or 3 was observed between the irradiated and control group while collagen content decreased in the irradiated versus the control group (10.05%+/-1.48% versus 31.92%+/-3.12%, respectively; p<0.001). The study supports the hypothesis that IVB associated with stenting induces late deleterious effects on the medial layer, characterized by formation of intramural neovessels, haemorrhages and a decrease in collagen content.

Animals↗

PubMed2003

Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis.

OBJECTIVES: To assess patients with different types of mutations of the beta myosin heavy chain (beta MHC) gene causing hypertrophic cardiomyopathy (HCM) and to determine the prognosis of patients according to the affected functional domain of beta MHC. DESIGN AND SETTING: Cohort study of subjects referred to an HCM clinic at an academic hospital. PATIENTS: 70 probands from the HCM clinic were screened for mutations of the beta MHC gene and 148 family members of the genotype positive probands were further assessed. The control group for the genetic studies consisted of 106 healthy subjects. MAIN OUTCOME MEASURES: Direct DNA sequencing was used to screen 70 probands for mutations of the beta MHC gene. Family members underwent genotypic and detailed clinical, ECG, and echocardiographic assessments. The survival of genotype positive subjects was evaluated according to the type of functional domain affected by the missense mutation and according to phenotypic characteristics. RESULTS: A mutation of the beta MHC gene was detected in 15 of 70 probands (21%). Of 148 family members studied in these 15 families, 74 were identified with a beta MHC defect. Eleven mutations were detected, including four novel mutations: Ala196Thr, Pro211Leu, Val404Leu, and Arg870Cys. Median survival was 66 years (95% confidence interval (CI) 64 to 77 years) in all affected subjects. There was a significant difference in survival between subjects according to the affected functional domain (p = 0.02). Significant independent predictors of decreased survival were the non-conservative (that is, associated with a change in the amino acid charge) missense mutations that affected the actin binding site (hazard ratio 4.4, 95% CI 1.6 to 11.8; p = 0.003) and those that affected the rod portion of beta MHC (hazard ratio 4.8, 95% CI 1.2 to 19.4; p = 0.03). No phenotypic characteristics were associated with decreased survival or cardiovascular morbidity. CONCLUSIONS: The type of beta MHC functional domain affected by the missense mutation is predictive of overall prognosis in HCM.

Adolescent↗

PubMed2003

Regulatory strategies to reduce tobacco addiction in youth.

Preventing tobacco addiction and achieving cessation in established users are the cornerstones of efforts to reduce tobacco use and disease. It has been increasingly recognised that reducing tobacco toxin exposure has theoretical potential to reduce disease in continuing tobacco users. This has been controversial because such approaches also carry the potential to undermine prevention and cessation. As complicated as harm reduction issues are for adults, they are still more complicated for youth. Harm reduction is not a singular approach, but rather a concept that encompasses an extremely diverse array of potential approaches. These carry equally diverse potential risks and benefits. The regulatory framework (for example, whether or not the Food and Drug Administration regulates the approach) is also predicted to be a major factor in determining the consequences of harm reduction approaches. This paper examines the various issues and potential approaches concerning the application of harm reduction to youth. We conclude that although some carry great risk, others may actually support broader tobacco control efforts to prevent tobacco use and foster cessation in youth and adults.

Adolescent↗

PubMed2003

[Application of risk stratification scores in acute myocardial infarction. Results of RICO (observation of infarction in the Ivory Coast)].

Several risk stratification scores for myocardial infarction have been developed in recent years, based on clinical trials. The object of this study was to assess the application of these scores in an unselected population of myocardial in farction in a French department. One thousand and fifty-four patients with acute myocardial infarction were included in the RICO observatory in the Côte d'Or. Those with ST elevation (SST), N = 746, had 30 day-mortality rates which increased with the TIMI and GUSTO scores (khi2 tendency, p < 0.001). There was a good discriminatory power of both these scores (correlations of 0.71 and 0.69 respectively). Similarly, logistic regression analysis showed a significant relationship between TIMI and GUSTO scores and 30 day mortality (p < 0.001). No correlation was observed between mortality and increased TIMI score in cases of infarction without ST elevation, N = 308, p = 0.344. Moreover, this score had a low discriminatory value in the study population with a correlation of 0.54. On the other hand, regression analysis showed a strong predictive value of the PURSUIT score in infarction without ST elevation for mortality. In addition, there was a correlation between death and the value of this score (p < 0.05). This score also showed a good discriminatory power with a correlation of 0.71. This study shows that, in an unselected population, risk stratification scores may be used as a routine in myocardial infarction, especially in cases with ST elevation.

Aged↗

PubMed2002

Exercise stress testing for detection of silent myocardial ischemia in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

The prevalence of silent myocardial ischemia (SMI) and the factors associated with SMI were evaluated in patients infected with human immunodeficiency virus (HIV) who had been receiving highly active antiretroviral therapy (HAART) for > or =12 months and did not have known coronary artery disease or cardiac symptoms. Patients prospectively underwent exercise stress testing. The prevalence of SMI was 11% (11 of 99 patients). Patients who had SMI were significantly older than were patients who did not (mean+/-SD, 51+/-8 years vs. 42+/-9 years; P=0.001) and were more likely to have trunk obesity (54% of patients vs. 17%; P=.004). A significant correlation was found between a positive exercise test result and obesity (correlation,.006), waist-to-hip ratio (.007), and glucose and cholesterol levels (.04; P=.03). In multivariate analysis, age, central fat accumulation, and cholesterol level were independent variables associated with the detection of SMI. Exercise testing might be recommended for patients with HIV who have central fat accumulation and hypercholesterolemia.

Adult↗

PubMed2002

[Beneficial effects of direct call to Emergency Medical Services on time delays and management of patients with acute myocardial infarction. The RICO (obseRvatoire des Infarctus de Côte-d'Or) data].

The influence of direct calls to specialized Emergency Medical Services in case of suspected myocardial infarction has not been extensively studied. The RICO registry is an exhaustive registry implemented in all six institutions participating in primary care of patients with acute myocardial infarction in one French administrative department (Côte-d'Or). From January 2001 to October 2001, 322 patients were admitted for acute myocardial infarction, among whom only 57 (18%) had directly called emergency medical services after the onset of symptoms. The baseline characteristics of patients who had directly called the emergency services were not different from those of the patients who had not. However, the time from symptom onset to first medical intervention (48 versus 105 minutes, p = 0.02) and from first medical intervention to hospital admission (60 versus 103 minutes, p = 0.02) were markedly shorter in patients who had directly called the emergency medical services. This resulted in a significant increase in the use of reperfusion therapy (70% versus 38%, p = 0.003), including a higher proportion of primary angioplasty (33% versus 20%, p = 0.04). This study documents the beneficial effect of a direct call to the Emergency Medical Services by the patients themselves. Too few patients, however use this opportunity and actions should be taken for informing the lay public of the benefits of this medical service.

Adult↗

PubMed2002

Hyperprolactinemia in asymptomatic patients is related to high molecular weight posttranslational variants or glycosylated forms.

Circulating human Prolactin (PRL) exists in different variants related to posttranslational modifications, dimerization or association with other serum proteins. Compared to monomeric prolactin these variants usually have little or no biologic activity and include BigBig (BB PRL), Big (B PRL), and Glycosylated forms (G PRL). The aim of the present study was to assess levels of BB PRL, B PRL, little PRL (L PRL) and G PRL in hyperprolactinemic patients with no menstrual alterations or galactorrhea. L PRL, B PRL, and BB PRL were identified by gel filtration chromatography on Sephadex G-100; G PRL and NG PRL were identified by chromatography on Concanavalin A Sepharose. PRL was measured by IRMA DPC. Eleven women, aged 22-50 yrs, were studied for: breast dysplasia (1), controlled hypothyroidism (3), dysmenorrhea (3), microadenoma follow-up (2), and gynecological control (2). Pituitary MRI was normal in all but one patient, who had a microadenoma discovered by Magnetic Resonance Imaging. Six patients had normal L PRL levels, and their hyper PRL was due to excess BPRL or BB PRL. Five patients had increased L PRL levels, but excess G PRL. Patients harboring molecular PRL variants do not present the symptoms typical of the hyperprolactinemic syndrome. Furthermore in patients with clinically controlled prolactinomas the presence of PRL variants should be ruled out to avoid an unnecessary increase of dopamine agonist dosage.

Adult↗

PubMed2001

Mild postischemic hypothermia is neuroprotective in the immature rat neocortex slice.

Mild hypothermia as an intervention after perinatal asphyxia may prevent neurological damage in the newborn. We used stimulus-induced field potentials to monitor recovery from oxygen and glucose deprivation (OGD) in neocortex slices of 6-8-day-old wistar rats. OGD after a latency of 10.7+/-2.1 min (mean+/-S.E.) resulted in an anoxic depolarisation with an amplitude of 5.4+/-2.4 mV. Mild hypothermia of 31 degrees C (vs. 35 degrees C in the control group) was applied for 60 min after end of OGD. The 20, 40, 60 and 80% recovery of the field potential amplitude was significantly faster in the hypothermia group in comparison to the control group. These data indicate that mild postischemic hypothermia may have neuroprotective effects after perinatal asphyxia.

Animals↗

PubMed2001

[Medico-economic impact of the Program of Medicalization of the Information System on hospital stay for myocardial infarction: influence of the quality of data collection and hospitalization length].

The aim of the Medicalisation Program of the Information System was to describe the activity of hospital for budget allocation. This work concerned the whole hospitalizations in the unit of intensive care of cardiology of Dijon for a myocardial infarction (MI) during the 1st half of 1998 (59 patients). The objectives of this study were: 1) the estimate of the real cost of MI management; 2) the comparison of this cost with the reference cost, determined from the data of the National Basis of Costs (BNC); 3) the economic impact of the quality of coding. The real global cost of MI was estimated at 2,323,542 FF (average by patient: 39,382 +/- 15,718 FF). Sixty eight per cent of the costs are directly related to the standing fixed overheads; in contrast, the medical and the therapeutic acts accounted for only 32% of the estimated real cost. A 52% over-estimation was highlighted between the estimated real cost and the cost of reference (p < 0.001). The errors of coding accounted for an under-estimation of only 3.6% of the cost of reference. The duration of hospitalization was significantly higher than the stay length taken from the national reference database (12.9 +/- 5.4 versus 9.2 +/- 2.1 days; p < 0.001), and was mainly responsible for these discrepancies of costs.

Costs and Cost Analysis↗

PubMed2001

Postischemic myocardial recovery and oxidative stress status of vitamin C deficient rat hearts.

OBJECTIVE: To investigate the role of vitamin C tissue content as a protective agent during myocardial ischemia-reperfusion injury, we have evaluated the postischemic functional recovery and free radical release of osteogenic disorder Shionogi (ODS) inherently scorbutic rat hearts and compared them to healthy Wistar rat hearts. METHODS: Isolated perfused hearts of ODS or Wistar rats underwent 30 min of a global total normothermic ischemia followed by 30 min of reperfusion. The lipid-soluble spin trap alpha-phenyl N-tert-butylnitrone (3 mM) was perfused upstream of the coronary bed. Functional parameters were recorded and samples of coronary effluents were analysed using electron spin resonance spectroscopy to characterise and quantify the amount of radical species released. RESULTS: From the onset of reperfusion, a large and long-lasting release of alkyl/alkoxyl radicals was detected, with a peak value of 29.0+/-3.2 nM obtained after 13 min, which was associated with a persistent contractile dysfunction. However, ODS rat hearts showed a higher myocardial recovery with lower left ventricular end diastolic pressure (44.34+/-1.74 vs. 55.03+/-1.57 mmHg for Wistar), higher recovery of rate pressure product (12.3+/-1.4 vs. 1.9+/-1.7x10(3) mmHg beats/min for Wistar) and shorter duration of contractile abnormalities during reperfusion (3.7+/-1.0 vs. 20.8+/-5.3 min for Wistar). Moreover, free radical release was identical in ODS rat hearts as compared to control Wistar rats. Ascorbic acid tissue content was significantly altered in ODS rats (31.9+/-3.3 vs. 591.0+/-54.9 mmol/g of tissue for Wistar) but superoxide dismutases, glutathion peroxidases and inducible heat shock protein 70 genes were up-regulated. CONCLUSIONS: This study shows that ascorbic-acid-deficient ODS rat hearts are more resistant to an ischemic insult than control Wistar rats, probably through the development of alternative protective defences, like the induction of heat shock proteins. These paradoxical results raise the question of the relative importance of each endogenous antioxidant in the cardiac resistance to ischemia-reperfusion injury.

Analysis of Variance↗

PubMed2001

Use of nonspecific cleavage products for protein sequence analysis as shown on calcyclin isolated from human granulocytes.

In this paper, analysis strategies developed for a sequencing problem concerning the identification of an S100 protein isolated from human granulocytes are discussed. The analysis of a trypsinized lyophilized sample suggested the presence of a number of peptides which are non-tryptic in origin. During purification of proteins from cell lysates nonspecific cleavage can be observed which may reflect biological processes and can become an unavoidable analytical problem. Current mass spectrometric software is evaluated for the analysis of nonspecific digests in this context. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), high-performance liquid chromatography (HPLC)-MS/MS, and selected ion monitoring (SIM)-MS/MS have been used for peptide analysis and in addition HPLC-MS was carried out for protein analysis leading to the detection of an N-terminal modification of the protein. The success of the study is mainly due to the careful investigation of nonspecific cleavage products. Data obtained from the routine mass spectrometric analysis of an in-gel-digest allowed the identification of this protein as S100 calcium-binding protein A6-calcyclin whose expression in granulocytes has not been described so far.

Amino Acid Sequence↗

PubMed2001

Long-term prognostic value of 201Tl single-photon emission computed tomographic myocardial perfusion imaging after coronary stenting.

BACKGROUND: The prognostic value of (201)Tl myocardial imaging has been demonstrated in several studies concerning patients with a known significant coronary artery disease. However, the evolution of a coronary stenosis after stenting is difficult to predict. This study was designed to assess the prognostic value of (201)Tl single-photon emission computed tomography (thallium SPECT) perfusion imaging in patients after intracoronary stenting. METHODS: One hundred fifty-two patients were studied. They were followed up during 40 +/- 13 (mean +/- SD) months after thallium SPECT. Stent-related events were studied after thallium stress testing and included cardiovascular death, myocardial infarction, and revascularization. Stress thallium imaging was performed 5 +/- 2 months after stenting, and ischemia was considered to be present if at least 2 contiguous segments were showing reversible defects. RESULTS: Only 3 (3%) among the 105 nonischemic patients had major cardiac events during the follow-up versus 13 (28%) of the 47 ischemic patients (P < .001) after thallium SPECT. The relative risk of major cardiac events for patients with significant ischemia was 10.5 compared with nonischemic patients (P < .001). Fourteen (30%) of the ischemic patients and 8 (8%) among the nonischemic patients underwent iterative revascularization (P < .001). Therefore, only 11 (10%) of the nonischemic patients had major cardiac events or revascularization compared with 24 (51%) of the ischemic patients (P < .001). CONCLUSIONS: Absence of ischemia on thallium SPECT imaging at 5 months after coronary stenting indicates a low risk for cardiovascular events or interventional procedure. These results may have important clinical implications in patient treatment.

Angioplasty, Balloon, Coronary↗

PubMed2001

Levels of nitric oxide in the heart after experimental myocardial ischemia.

The effect of myocardial ischemia on nitric oxide (NO) production is controversial in part because of indirect NO quantification. In the present study, direct quantification of NO was investigated in an in vivo rat model of myocardial ischemia (MI). A NO spin-trapping technique using electron spin resonance (ESR) spectroscopy was used to study NO production in the ischemic and in the nonischemic area of the rat heart 2, 8, or 24 h after left main coronary artery ligation. The method was based on the trapping of NO by a metal-chelator complex consisting of N-methyl-D-glucamine-dithiocarbamate (MGD) and Fe(II) to form a stable NO-FeMGD complex that gives rise to a characteristic triplet ESR spectrum. This metal-chelator complex was administered half an hour before sacrifice of the rats. A large and time-dependent increase of the ESR signal corresponding to the NO-FeMGD complex was observed 8 h (11.6 +/- 0.9 arbitrary units [AU]) and 24 h (29.7 +/- 2.9 AU) in the ischemic area after MI. On the contrary, no ESR triplet was observed in the nonischemic region of the heart and in sham-operated rats. NO blood derivative levels (nitrosylhemoglobin and plasma nitrites and nitrates) were unchanged compared with sham-operated rats. Previous administration of aminoguanidine, a NO synthase inhibitor, in animals subjected to a 24-h ischemia resulted in a complete abolition in the NO-FeMGD spectrum in the ischemic area. These findings directly demonstrated an increase of the NO-FeMGD levels during in vivo myocardial ischemia that appeared to be specifically localized in the ischemic area.

Animals↗

PubMed2001

Inferences on force transmission from muscle fiber architecture of the canine diaphragm.

Functional properties of the diaphragm are mediated by muscle structure. Modeling of force transmission necessitates a precise knowledge of muscle fiber architecture. Because the diaphragm experiences loads both along and transverse to the long axes of its muscle fibers in vivo, the mechanism of force transmission may be more complex than in other skeletal muscles that are loaded uniaxially along the muscle fibers. Using a combination of fiber microdissections and histological and morphological methods, we determined regional muscle fiber architecture and measured the shape of the cell membrane of single fibers isolated from diaphragm muscles from 11 mongrel dogs. We found that muscle fibers were either spanning fibers (SPF), running uninterrupted between central tendon (CT) and chest wall (CW), or were non-spanning fibers (NSF) that ended within the muscle fascicle. NSF accounted for the majority of fibers in the midcostal, dorsal costal, and lateral crural regions but were only 25-41% of fibers in the sternal region. In the midcostal and dorsal costal regions, only approximately 1% of the NSF terminated within the fascicle at both ends; the lateral crural region contained no such fibers. We measured fiber length, tapered length, fiber diameters along fiber length, and the taper angle for 271 fibers. The lateral crural region had the longest mean length of SPF, which is equivalent to the mean muscle length, followed by the costal and sternal regions. For the midcostal and crural regions, the percentage of tapered length of NSF was 45.9 +/- 5.3 and 40.6 +/- 7.5, respectively. The taper angle was approximately 0.15 degrees for both, and, therefore, the shear component of force was approximately 380 times greater than the tensile component. When the diaphragm is submaximally activated, as during normal breathing and maximal inspiratory efforts, muscle forces could be transmitted to the cell membrane and to the extracellular intramuscular connective tissue by shear linkage, presumably via structural transmembrane proteins.

Animals↗

PubMed2001

Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs.

Recent reports indicate that genes with tissue-restricted expression, including those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512), are transcribed in the thymus. The reported modulation of diabetes susceptibility by genetically determined differences in thymic insulin levels and studies in transgenic mice provide correlative and functional evidence that thymic expression of peripheral proteins is crucial for immunological self-tolerance. However, there are no specific data about the existence, tissue distribution, phenotype, and function of those cells that express insulin and other self-antigens in the human thymus. We find that the human thymus harbors specialized cells synthesizing (pro)insulin, GAD, and IA-2, mainly localized in the medulla, and we demonstrate such cells also in peripheral lymphoid organs (spleen and lymph nodes). Phenotypic analysis qualifies these cells as antigen-presenting cells (APCs), including both dendritic cells and macrophages. These cells often appear surrounded by apoptotic lymphocytes, both in thymus and spleen, and may therefore be involved in the deletion of autoreactive lymphocytes. Our findings demonstrate the existence of, and define the tissue distribution and phenotype of, a novel subset of APCs expressing self-antigens in human lymphoid organs that appear to be involved in the regulation of self-tolerance throughout life.

Adolescent↗

PubMed2001

Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen.

Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping of the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models. It is unclear why patients lose tolerance to IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated with type 1 diabetes. We report that alternative splicing determines differential IA-2 expression in islets compared with thymus and spleen. Islets express full-length mRNA and two alternatively spliced transcripts, whereas thymus and spleen exclusively express an alternatively spliced transcript lacking exon 13. This encodes for the transmembrane (TM) and juxta-membrane (JM) domains that comprise several type 1 diabetes target epitopes, supporting the concept that tolerance to IA-2 epitopes not expressed in lymphoid organs may not be achieved. We propose differential splicing as a regulatory mechanism of gene expression playing a permissive role in the development of autoimmune responses to IA-2. Our findings also show that candidate gene expression studies can help in dissecting the complex genetic determinants of a multifactorial disease such as type 1 diabetes.

Adult↗

PubMed2001

[Secondary effects of brachytherapy in the treatment of coronary restenosis].

Brachytherapy is proposed for the treatment or prevention of coronary restenosis with encouraging results, especially in intra-stent restenosis. The results of the first clinical studies show benefit, for example those of the American SCRIPPS trial with a 3 year follow-up. However, recent reports in the literature have described secondary effects associated with this technique: 1) stenoses occurring at the limits of the irradiated segments which are attributed to a proliferative effect of low doses on damaged tissue; 2) late occlusions at the irradiated site: their incidence is estimated at 9% at 6 months. The mechanisms of these thromboses are not understood but delayed re-endothelialisation probably plays a rôle; 3) finally, irradiation is associated with uncovered dissection probably related to delayed healing. Other long-term trials are necessary to provide a more complete assessment of the secondary effects of brachytherapy, especially with regards to their mechanisms, prevention and treatment.

Angioplasty↗