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Biomedical subjects

B J Meyer

Publications and source records attributed to B J Meyer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a case-control study.

BACKGROUND: The platelet membrane glycoprotein Ia/IIa plays a major part in platelet function as a primary receptor for collagen. A previous report showed a variation of glycoprotein Ia/IIa receptor density and function associated with two silent and linked polymorphisms (807C/T and 873G/A) within the glycoprotein Ia gene. Because platelet thrombus formation is implicated in the pathogenesis of acute myocardial infarction, we investigated these polymorphisms among patients who had had a myocardial infarction. METHODS: We did a 2/1 case-control study including 177 patients (median age 57.0 [range 32-72] years) and 89 controls with same age and sex. Distributions of the 807C/T and 873G/A polymorphisms were investigated by genotyping DNA by PCR, single-strand conformation polymorphism analysis, and sequencing. FINDINGS: The prevalence of the homozygous 807T/873A genotype was 2.9 times higher among patients with myocardial infarction than among controls (16.4% vs 5.6%, p=0.022). There was an association between patients homozygous for the 807T/873A allele and myocardial infarction (odds ratio 3.3 [95% CI 1.2-8.8]), which was strongest in a subgroup of smokers. The homozygous 807T/873A genotype remained an independent risk factor for myocardial infarction (p=0.005) when age, sex, smoking, hypertension, diabetes, body-mass index, LDL-cholesterol and HDL-cholesterol, and fibrinogen were adjusted for by logistic regression. INTERPRETATION: The 807T/873A homozygosity of the platelet glycoprotein Ia/IIa gene polymorphism, associated with differences in surface collagen receptor density and activity, appears to be an independent risk factor for acute myocardial infarction. Our findings need to be confirmed in a larger, prospective study that includes patients from different populations and cardiovascular risk groups.

Adult↗
PubMed1999

Economic assessment of tirofiban in the management of acute coronary syndromes in the hospital setting: an analysis based on the PRISM PLUS trial.

AIMS: We analysed whether generalized use of tirofiban plus heparin and aspirin might save direct healthcare costs, as compared with heparin and aspirin alone, in patients with acute coronary ischaemic syndromes in Switzerland. METHODS AND RESULTS: We conducted an incremental cost-consequence analysis from the perspective of the admitting hospital for the period of the first 7 days. Costs were analysed for the management of refractory ischaemic conditions and myocardial infarctions, including incremental days on the general ward or intensive care unit, as well as necessary revascularization procedures, and expressed in Swiss francs (CHF) and European currency units (ECU). Drug costs were based on a loading dose of 0.4 micro x kg(-1) x min(-1)and a maintenance dose of 0.1 micro x kg(-1) x min(-1)for tirofiban at a cost of CHF 273.55 (ECU 166.50) per vial. Heparin was administered at a loading dose of 5000 U and a maintenance dose of 1000 U x h(-1). All calculations were standardized to 100 treated patients. The costs of managing ischaemic complications were based on typical practice patterns in Swiss hospitals. The incremental costs per patient of managing unstable angina patients with recurrent ischaemia or myocardial infarction were calculated as CHF 23 325 (ECU 14 198) and CHF 18 599 (ECU 11 321), respectively. The incremental drug costs amounted to CHF 82 065 (ECU 49 954). The additional use of tirofiban resulted in net savings of CHF 54 899 (ECU 33 418) per 100 patients, achieved through a reduction in the cost of treating refractory ischaemic conditions (CHF 79 306, ECU 48 275) and myocardial infarctions (CHF 57 658, ECU 35 097). CONCLUSION: Tirofiban is cost-saving in acute coronary ischaemic syndromes and improves the economics of managing these patients during the initial hospitalization.

Angina, Unstable↗
PubMed1999

The primary sex determination signal of Caenorhabditis elegans.

An X chromosome counting process determines sex in Caenorhabditis elegans. The dose of X chromosomes is translated into sexual fate by a set of X-linked genes that together control the activity of the sex-determination and dosage-compensation switch gene, xol-1. The double dose of X elements in XX animals represses xol-1 expression, promoting the hermaphrodite fate, while the single dose of X elements in XO animals permits high xol-1 expression, promoting the male fate. Previous work has revealed at least four signal elements that repress xol-1 expression at two levels, transcriptional and post-transcriptional. The two molecularly characterized elements include an RNA binding protein and a nuclear hormone receptor homolog. Here we explore the roles of the two mechanisms of xol-1 repression and further investigate how the combined dose of X signal elements ensures correct, sex-specific expression of xol-1. By studying the effects of increases and decreases in X signal element dose on male and hermaphrodite fate, we demonstrate that signal elements repress xol-1 cumulatively, such that full repression of xol-1 in XX animals results from the combined effect of individual elements. Complete transformation from the hermaphrodite to the male fate requires a decrease in the dose of all four elements, from two copies to one. We show that both mechanisms of xol-1 repression are essential and act synergistically to keep xol-1 levels low in XX animals. However, increasing repression by one mechanism can compensate for loss of the other, demonstrating that each mechanism can exert significant xol-1 repression on its own. Finally, we present evidence suggesting that xol-1 activity can be set at intermediate levels in response to an intermediate X signal.

Animals↗
PubMed1999

Australian food sources and intakes of omega-6 and omega-3 polyunsaturated fatty acids.

BACKGROUND/AIMS: Both omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) are recognised as essential nutrients in the human diet, yet we have little information on the extent to which different food sources contribute to their intake. The aim of the present study was to ascertain the daily intakes and food sources of omega-6 and omega-3 PUFAs in our local community. METHODS: Three-day food records were obtained from 83 healthy adults living in the Illawarra region of New South Wales. The PUFA composition of the foods which they consumed was derived from food composition tables and recently published food analysis data. RESULTS: Polyunsaturated margarine, nuts/seeds, bread, snacks/desserts and takeaway foods were important sources of omega-6 PUFAs, while canola oil and margarine, takeaway foods, snacks/desserts and bread were sources of alpha-linolenic acid (LNA), an omega-3 PUFA. As expected, fish was the main source of the very long chain (VLC) omega-3 PUFAs, i.e. eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), to which significant health benefits are attributed. An unexpected finding, however, was that, due to the large amount eaten, meat was also a major contributor (29%) to the dietary intake of VLC omega-3 PUFAs. Median intakes of omega-6 and omega-3 PUFAs were 9.9 and 1.2 g/day, respectively, resulting in a dietary omega-6:omega-3 ratio of 8:1. The median intake of VLC omega-3 PUFA was 0.18 g/day. CONCLUSION: We have identified food sources and intakes of PUFAs for an Australian subpopulation differentiating between omega-6 and omega-3 PUFAs. Whilst canola and fish were the primary sources of LNA and VLC omega-3 PUFAs respectively, we found that meat made a significant contribution to VLC omega-3 PUFA intake.

Adult↗
PubMed1998

The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex.

Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.

Amino Acid Sequence↗
PubMed1998

Dissolution of mural thrombus by specific thrombin inhibition with r-hirudin: comparison with heparin and aspirin.

BACKGROUND: The presence of residual mural thrombus may predispose to recurrent thrombotic events in acute coronary syndromes. The purpose of this study was to evaluate the effects of antithrombotic and antiplatelet agents on a preformed, fresh mural thrombus during growth of thrombus. METHODS AND RESULTS: A fresh mural thrombus was formed by perfusing severely injured arterial wall with porcine blood for 5 minutes at a shear rate of 1690 s(-1). Thrombus formation was measured by morphometric analysis (mm2/mm). The average size of a mural thrombus formed in 5 minutes was 0.14+/-0.03 mm2/mm. Progression of thrombus growth within 10 minutes triggered by the preformed thrombus was evaluated in pigs treated with r-hirudin (1 mg/kg per hour i.v.) as a probe for thrombin, high-dose heparin (250 IU/kg per hour i.v.), moderate-dose heparin (100 IU/kg per hour), moderate-dose heparin (100 IU/kg per hour) plus aspirin, aspirin alone (5 mg/kg i.v.), and placebo. Hirudin was associated with a significant decrease (48%) of mural thrombus area and significantly reduced growth of thrombus (0.07+/-0.01), even compared with the highest dose of heparin (0.15+/-0.03), although at lower levels of anticoagulation. Inhibition of growth of thrombus with heparin was dose dependent, showing an inverse correlation of thrombus area with mean plasma heparin concentrations (r=.77, P=.0001). Thrombus size was unchanged by aspirin (0.29+/-0.07) compared with controls (0.28+/-0.07). CONCLUSIONS: Direct inhibition of thrombin activity with r-hirudin completely inhibits growth of thrombus, causes dissolution of a preexisting mural thrombus, and is more effective at lower levels of anticoagulation than the highest dose of heparin at shear rates typical of a moderate coronary stenosis.

Animals↗
PubMed1998

MIX-1: an essential component of the C. elegans mitotic machinery executes X chromosome dosage compensation.

We show that a functional component of the C. elegans mitotic machinery regulates X chromosome gene expression. This protein, MIX-1, is a member of the dosage compensation complex that associates specifically with hermaphrodite X chromosomes to reduce their gene expression during interphase. MIX-1 also associates with all mitotic chromosomes to ensure their proper segregation. Both dosage compensation and mitosis are severely disrupted by mix-1 mutations. MIX-1 belongs to the SMC protein family required for mitotic chromosome condensation and segregation in yeast and frogs. Thus, an essential, conserved component of mitotic chromosomes has been recruited to the dosage compensation process. Rather than dosage compensation and mitosis being achieved by two separate sets of related genes, these two processes share an identical component, indicating a common mechanism for establishing higher order chromosome structure and proper X chromosome gene expression.

Amino Acid Sequence↗
PubMed1998

Interventional cardiology in Europe 1994. Working Group Coronary Circulation of the European Society of Cardiology.

The working group Coronary Circulation of the European Society of Cardiology conducts an annual survey of cardiac interventions in Europe with the support of the national societies of cardiology. A detailed questionnaire about cardiac interventions performed during 1994 was mailed to all members of the European Society of Cardiology. Incomplete or absent data from eight national members precluded their inclusion in the final analysis. Thus, this report summarizes the cardiac interventions performed during 1994 in 29 of 37 members of the European Society of Cardiology, representing a total population of approximately 490 million inhabitants. CORONARY ANGIOGRAPHY: A total of 922,687 coronary angiograms were reported during 1994, representing an increase of 22% compared with 1993 and of 35% compared with 1992. The mean incidence of coronary angiograms was 1881/10(6) inhabitants, ranging from 4417/10(6) inhabitants in Germany to 35/10(6) inhabitants in Romania, Germany, France, Great Britain, and Italy with 50% of the European population performed 73% of all cardiac interventions. CORONARY ANGIOPLASTY: During 1994, a total of 224,722 coronary angioplasty (PTCA) procedures were reported in Europe, an increase of 22% compared with 1993 and of 52% compared with 1992. Adjusted per capita, the mean incidence of coronary angioplasty was 458/10(6) inhabitants, ranging from 1091/10(6) inhabitants in Germany to 6/10(6) inhabitants in Romania. On average, the ratio PTCA per coronary angiogram was 0.24, ranging from 0.37 in the Netherlands to 0.06 in Cyprus. Ad hoc PTCA accounted for 22% of all PTCA cases. The majority (81%) of PTCAs were restricted to a single vessel. Major complications were reported in 2% of patients undergoing PTCA, including death (0.3%), myocardial infarction (1.0%) and need for emergency coronary artery bypass grafting (0.7%). CORONARY STENTING: Coronary stents were utilized in 21,599 coronary interventions during 1994, an increase of 235% compared with 1993 and thus representing the fastest growth in interventional cardiology. The number of European countries employing stents during coronary angioplasty grew from 14 during 1993 to 24 during 1994. Elective use (38%) became the most frequent indication for coronary stenting during 1994, replacing bail-out stenting as the primary indication during 1993. OTHER NEW DEVICES: Other new interventional therapeutic devices were employed in 8827 cases. Only the Rotablator was used more frequently during 1994 as compared with 1993. All other new therapeutic devices showed a decline. Coronary ultrasound was utilized in 3032 interventions and coronary angioscopy in 304 cases during 1994. NON-CORONARY INTERVENTIONS: Valvuloplasty remained the most frequent non-coronary intervention in Europe during 1994 with a total of 2622 mitral. 609 pulmonary and 506 aortic valvuloplasties. CATHETERIZATION FACILITIES: The number of facilities per 10(6) inhabitants performing invasive cardiac procedures in Europe during 1994 ranged from 7.7 in Iceland to 0.2 in Romania (European mean 2.9). The number of trained operators per 10(6) inhabitants ranged from 24 in Germany to 0.4 in Romania (European mean 10). During 1994, a mean of 701 coronary angiograms and 170 PTCAs were performed per catheterization facility in Europe (range: 1052 coronary angiograms and 293 PTCAs per facility in Norway to 218 coronary angiograms and 37 PTCAs per facility in Romania). CONCLUSIONS: The number of both coronary angiograms and coronary angioplasties continues to grow at an annual rate of approximately 20% in Europe. There is a wide range in the amount of revascularization procedures performed between western and eastern European countries. However, countries with the lowest numbers of coronary angiograms and coronary angioplasties, e.g. Romania, also show the fastest annual growth. About one quarter of all patients undergoing coronary angiography are subsequently revascularized by coronary angioplasty. (ABSTRACT TRUN

Angioplasty, Balloon, Coronary↗
PubMed1998

Antithrombotic drugs: insights from cardiology.

The primary purpose of this overview is to provide an update on the newer antiplatelet drugs evaluated in clinical trials and introduced in clinical practice of modern cardiology. Despite the remarkable clinical developments with the use of new antiplatelet drugs, several fundamental issues remain unresolved. Some of the observed safety/efficacy problems in major clinical trials can be directly attributed to the lack of careful phase II studies where issues such as monitoring, pharmacological profiles, and individual response variations were not considered sufficiently. Nevertheless, none of the available antiplatelet agents meet all the criteria of an ideal antiplatelet agent. Aspirin has been the standard reference agent in cardiovascular disease. However, it is a weak and nonselective antiplatelet compound and is unable to interfere substantially with the thrombogenic activity of a fresh mural thrombus of a stenosed vessel. The newer antiplatelet drug classes such as the ADP receptor blockers (ticlopidine, clopidogrel) and the platelet glycoprotein IIb/IIIa receptor inhibitors produce their therapeutic effects by distinct mechanisms which differ from aspirin. Large clinical trials have documented their efficacy in acute coronary syndromes associated with intracoronary thrombus formation. The future challenge is to evaluate long-term treatment strategies which are equally safe but distinctly more effective than aspirin, e.g. a combination therapy with aspirin and clopidogrel or oral GP IIb/IIIa receptor antagonists.

Cardiology↗
PubMed1998

[Prevention of thrombosis in heart valve diseases].

Thromboembolism and bleeding during therapeutic anticoagulation are the major chronic risks for patients with native valvular heart disease and mechanical prosthetic heart valves. The recommendations for the prevention of thromboembolic events and bleeding complications are discussed. In particular, risk factors for thromboembolic events, indications and intensity of antithrombotic therapy, and approaches to practical problems of oral anticoagulation for patients with valvular heart disease are outlined.

Anticoagulants↗
PubMed1997

Caenorhabditis elegans rab-3 mutant synapses exhibit impaired function and are partially depleted of vesicles.

Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.

Aldicarb↗
PubMed1997

Magnum wire for percutaneous coronary balloon angioplasty in 800 total chronic occlusions.

The experience in consecutive procedures with 800 recanalization attempts of chronic total coronary occlusions using the Magnum wire was analyzed from a prospectively constituted computerized database. The data confirm that the Magnum wire, generally used as a primary intervention for occlusive angioplasty at our centers, is competitive with conventional systems in this setting.

Angioplasty, Balloon, Coronary↗
PubMed1997

X-chromosome-counting mechanisms that determine nematode sex.

Sex is determined in Caenorhabditis elegans by an X-chromosome-counting mechanism that reliably distinguishes the twofold difference in X-chromosome dose between males (1X) and hermaphrodites (2X). This small quantitative difference is translated into the 'on/off' response of the target gene, xol-1, a switch that specifies the male fate when active and the hermaphrodite fate when inactive. Specific regions of X contain counted signal elements whose combined dose sets the activity of xol-1. Here we ascribe the dose effects of one region to a discrete, protein-encoding gene, fox-1. We demonstrate that the dose-sensitive signal elements on chromosome X control xol-1 through two different molecular mechanisms. One involves the transcriptional repression of xol-1 in XX animals. The other uses the putative RNA-binding protein encoded by fox-1 to reduce the level of xol-1 protein. These two mechanisms of repression act together to ensure the fidelity of the X-chromosome counting process.

Animals↗
PubMed1997

Magnum wire for angioplasty of total and non-total coronary lesions.

The magnum wire is a stiff-shaft, blunt-tip wire constructed for recanalisation during angioplasty. Smaller series have demonstrated superior qualities compared to conventional wires. The purpose of this study was to analyze its feasibility in a larger number of procedures. A single centre database analysis identified the use of Magnum wire during 443 procedures accounting for 26% of all angioplasties from October 1992 to February 1995. There were 347 total occlusions and 222 non-total lesions. Technical success was 69% in total and 90% in non-total lesions, whereas angiographic success was 58% and 75%, respectively. Stents were successfully implanted in 48 lesions; in 29 (8%) total occlusions and 19 (9%) non-total lesions. The total occlusion-related complication rate was 1.7%. Acute closure occurred in 4.1% of non-total lesions. In conclusion, Magnum wire is a feasible tool for angioplasty of total occlusions and severe stenoses. It is a cheap, simple and safe method for recanalisation.

Adult↗
PubMed1997

[Current trends in coronary angioplasty].

Coronary angioplasty still is an area of intensive development. The publication of the BARI data confirms and consolidates previous findings that balloon angioplasty and bypass surgery are equivalent in terms of mortality and major complications over a mid-term follow-up period. However, balloon angioplasty has a high rate of reinterventions, and is not recommended in diabetic patients with multivessel disease. The question, whether direct PTCA is a better treatment strategy of acute myocardial infarction than thrombolytic therapy remains unsettled despite a slight advantage for direct PTCA in several small randomized trials. The role of coronary stents has continuously expanded over the last years, as a tool against acute as well as long-term complications of angioplasty. This success is partly due to the finding that antiplatelet agents such as ticlopidine offer an effective protection against subacute stent thrombosis. The introduction of the GP IIb/IIIa platelet receptor blockers has provided another powerful tool against acute thrombotic complications, leading to a more aggressive interventional strategy in acute coronary syndromes. The development of alternative "devices" has further slowed down because of repeated publication of negative clinical results. Although different forms of laser energy applications, of local drug delivery, and of local irradiation are interesting research areas, their current impact on clinical practice is small.

Angioplasty, Balloon, Coronary↗
PubMed1997

A novel type of defective viral genome suggests a unique strategy to establish and maintain persistent lymphocytic choriomeningitis virus infections.

Defective interfering RNAs have long been thought to be a causal factor of persistent RNA virus infections. Here we describe a novel type of defective genome of lymphocytic choriomeningitis virus and the unique mechanism by which these RNAs appear to contribute to the establishment and maintenance of persistent infection. The defective genomes have short deletions in the untranslated regions at their termini and additional nontemplated terminal nucleotides. This and previous work from our laboratory suggested that the RNAs were competent for replication but not for transcription. From experiments using a technique to unambiguously determine the sequences of individual RNA termini, it appears that some truncated RNAs can be repaired. The data suggest that the loss or gain of nucleotides from the RNA termini during the course of infection is the mechanism for establishing and maintaining persistence.

Animals↗
PubMed1997

SDC-3 coordinates the assembly of a dosage compensation complex on the nematode X chromosome.

X chromosome expression in C. elegans is controlled by a chromosome-wide regulatory process called dosage compensation that specifically reduces by half the level of transcripts made from each hermaphrodite X chromosome. This process equalizes X expression between the sexes (XX hermaphrodites and XO males), despite their two-fold difference in X chromosome dose, and thereby prevents sex-specific lethality. Dosage compensation is achieved by a protein complex that associates with X in a sex-specific fashion to modulate gene expression. SDC-3, a protein that coordinately controls both sex determination and dosage compensation, activates dosage compensation by directing the dosage compensation protein complex to the hermaphrodite X chromosomes. We show that SDC-3 coordinates this assembly through its own sex-specific association with X. SDC-3 in turn requires other members of the dosage compensation gene hierarchy for its stability and its X localization. In addition, SDC-3 requires its own zinc finger motifs and an amino-terminal region for its X association. Our experiments suggest the possible involvement of zinc finger motifs in X chromosome recognition and the amino-terminal region in interactions with other dosage compensation proteins.

Animals↗