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Biomedical subjects

K Miedema

Publications and source records attributed to K Miedema.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic value of admission glucose and glycosylated haemoglobin levels in acute coronary syndromes.

BACKGROUND: Admission hyperglycaemia is associated with poorer prognosis in patients with an acute coronary syndrome (ACS). Whether hyperglycaemia is more important than prior long-term glucose metabolism, is unknown. AIM: To investigate the prognostic value of admission glucose and HbA(1c) levels in patients with ACS. METHODS: We measured glucose and HbA(1c) at admission in 521 consecutive patients with suspected ACS. Glucose was categorized as <7.8 (n = 305), 7.8-11.0 (n = 138) or > or =11.1 mmol/l (n = 78); HbA(1c) as <6.2% (n = 420) or > or =6.2% (n = 101). Mean follow-up was 1.6 +/- 0.5 years. RESULTS: The diagnosis of ACS was confirmed in 332 patients (64%), leaving 189 (36%) with atypical chest pain. In ACS patients, mortality by glucose category (<7.8, 7.8-11.0 or > or =11.1 mmol) was 9%, 8% and 25%, respectively (p = 0.001); mortality by HbA(1c) category (<6.2% vs. > or =6.2%) was 10% vs. 17%, respectively (p = 0.14). On multivariate analysis, glucose category was significantly associated with mortality (HR 3.0, 95% CI 1.1-8.3), but HbA(1c) category was not (HR 1.5, 95%CI 0.6-4.2). DISCUSSION: Elevated admission glucose appears more important than prior long-term abnormal glucose metabolism in predicting mortality in patients with suspected ACS.

Aged↗
PubMed2005

[Diagnosis of diabetes mellitus: limited use for portable blood-glucose measuring devices].

In the Netherlands, guidelines for the diagnosis of diabetes mellitus are confusing and differ from the international guidelines. Capillary blood-glucose testing using a blood-glucose device is allowed used as a diagnostic tool, although this test is imprecise. The Dutch laboratories measure blood-glucose concentrations by a more precise accurate method, but sometimes measure glucose levels in capillary whole blood and sometimes in venous plasma. These results are not comparable, because the results of capillary measurements are lower than the plasma measurements. In daily practice, health-care professionals are using different methods and are often not aware of the differences in glucose values that may result. They do not realise that glucose devices and laboratory glucose measurements may differ and that capillary- and plasma-glucose values are not interchangeable. Uniformity within the Dutch laboratories with regard to the glucose measurements is urgently needed, as is revision of the Dutch guidelines concerning the diagnosis of diabetes mellitus. This should be based solely on venous plasma-glucose values determined in a laboratory. Portable blood-glucose devices should not be used as a diagnostic tool for diabetes mellitus. These should only be used for blood-glucose control monitoring during treatment or as a screening tool.

Blood Glucose↗
PubMed2005

Dysglycemia in suspected acute coronary syndromes.

BACKGROUND: Apart from diabetes itself, even minor glycometabolic dysregulation may be associated with an increased risk of cardiovascular disease. We analyzed the prevalence and predictive value of glycometabolic disturbances in patients with a suspected acute coronary syndrome (ACS). METHODS: In a prospective follow-up study, admission glucose and Hba1C levels in all consecutive patients with suspected ACS were measured. Dysglycemia was defined as a Hba1C of 5.6-6.1% with a non-fasting glucose above 7.8 mmol/L. Both predictors of glycometabolic disturbances and the predictive value of glycometabolic disturbances were studied. RESULTS: Of the 521 patients with a suspected ACS who were included in the study, 332 (64%) had an ACS and 189 (36%) had atypical chest pain. A total of 115 patients (22%) had diabetes and 65 (13%) had dysglycemia. Patients with diabetes or dysglycemia had an increased risk of a confirmed diagnosis of ACS (RR 2.3, 95% CI 1.5-3.4). Multivariate analyses did not change these findings. CONCLUSIONS: One in three patients with suspected ACS had a glucose metabolism disturbance. Glycometabolic disturbance was strongly associated with a confirmed diagnosis of ACS. Whether intensive treatment of patients with disturbed glucose metabolism may improve long-term prognosis needs to be assessed.

Journal Article↗
PubMed2004

Towards worldwide standardisation of HbA1c determination.

Haemoglobin A(1)c (HbA(1)c) or glycohaemoglobin is one of the most important parameters in the management of patients with diabetes mellitus, but to date there is no international standard for determining HbA(1)c. Most of the routine HbA(1)c assays are standardised against one of the local standardisation schemes like the NGSP (USA) and other schemes (Japan, Sweden). Still, results of HbA(1)c tests diverge considerably, as do the accompanying clinical decision limits. The IFCC Working Group on HbA(1)c Standardisation has developed a reference method and also set up a reference system for HbA(1)c, in which the analyte is defined as beta-N-glycated haemoglobin. This reference system consists of a network of reference laboratories that uses the reference methods and certified reference materials for optimal measurement of HbA(1)c in human blood. The main task of the network is to assign values to secondary reference materials, to be used by manufacturers of routine HbA(1)c assays to calibrate their assays. The high specificity of the reference method results in lower HbA(1)c values in blood samples, since the unspecific components falsely identified as HbA(1)c in routine methods are not measured by the reference method. The reference range for the new reference method was determined as 3 to 4% and the clinical decision limits were translated from existing guidelines: goal of treatment 5% HbA(1)c, change of therapy advised at HbA(1)c greater than 6%. Despite these lower values, worldwide implementation of the IFCC reference system for HbA(1)c is recommended, in order to end the great divergence in HbA(1)c results, with which physicians and patients are confronted today.

Biomarkers↗
PubMed2003

[The troponin assay in a cardiac emergency unit: especially to exclude severe cardiac risk].

OBJECTIVE: To determine the value in daily practice of a troponin assay for triage of patients with chest pain. DESIGN: Retrospective and descriptive. METHOD: All patients in whom troponin T was measured after at least six hours after complaints began during the first three months of 2001 in the cardiac emergency unit of the Isala Clinics, location Weezenlanden, Zwolle, the Netherlands, were included. Cardiac events occurring within 30 days after the troponin assay were recorded retrospectively. RESULTS: All 350 included patients were followed for 30 days. An elevated troponin level was found in 51 patients (15%). At 30 days, 27 of these 51 patients had had a myocardial infarction or had died. Apart from these 27 patients, a revascularisation procedure was performed in nine patients. In the remaining 15 patients with an elevated troponin level, another reason for myocardial damage was found. In 40 patients in whom the troponin assay was negative, coronary artery disease was diagnosed later. The negative predictive value for myocardial infarction or death within 30 days was 98%. CONCLUSION: A troponin assay, performed six hours or more after the onset of cardiac symptoms, appears to be a safe method to exclude patients with severe coronary artery disease resulting in myocardial necrosis and an elevated risk of death. An elevated troponin level was always associated with myocardial damage, but not always with coronary artery disease. Therefore, there must be a clear indication for requesting a troponin assay, and one should always keep in mind that a normal troponin level does not exclude coronary artery disease.

Biomarkers↗
PubMed1999

Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction.

BACKGROUND: As compared with thrombolytic therapy, primary coronary angioplasty results in a higher rate of patency of the infarct-related coronary artery, lower rates of stroke and reinfarction, and higher in-hospital or 30-day survival rates. However, the comparative long-term efficacy of these two approaches has not been carefully studied. METHODS: We randomly assigned a total of 395 patients with acute myocardial infarction to treatment with angioplasty or intravenous streptokinase. Clinical information was collected for a mean (+/-SD) of 5+/-2 years, and medical charges associated with the two treatments were compared. RESULTS: A total of 194 patients were assigned to undergo primary angioplasty, and 201 to receive streptokinase. Mortality was 13 percent in the angioplasty group, as compared with 24 percent in the streptokinase group (relative risk, 0.54; 95 percent confidence interval, 0.36 to 0.87). Nonfatal reinfarction occurred in 6 percent and 22 percent of the two groups, respectively (relative risk, 0.27; 95 percent confidence interval, 0.15 to 0.52). The combined incidence of death and nonfatal reinfarction was also lower among patients assigned to angioplasty than among those assigned to streptokinase, with a relative risk of 0.13 (95 percent confidence interval, 0.05 to 0.37) for early events (within the first 30 days) and a relative risk of 0.62 (95 percent confidence interval, 0.43 to 0.91) for late events (after 30 days). The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group. Total medical charges per patient were lower in the angioplasty group (16,090 dollars) than in the streptokinase group (16,813 dollars, P=0.05). CONCLUSIONS: During five years of follow-up, primary coronary angioplasty for acute myocardial infarction was associated with lower rates of early and late death and nonfatal reinfarction, fewer hospital readmissions for ischemia or heart failure, and lower total medical charges than treatment with intravenous streptokinase.

Analysis of Variance↗
PubMed1999

RADHA--a new male germ line-specific chromosomal protein of Drosophila.

A new chromosomal protein - RADHA - of Drosophila is described that is specific for the male germ line. It is encoded by a single-copy gene, located in the region 96C-D of D. melanogaster polytene chromosomes. Transcription of the radha gene is restricted to the primary spermatocyte stage. The protein initially accumulates in some of the Y-chromosomal lampbrush loops. After meiosis it is found in the nuclei of spermatids and might be involved in chromatin rearrangement processes in the male germ line. RADHA is a basic protein with a C-terminal leucine zipper region and several segments capable of forming coiled-coil structures.

Amino Acid Sequence↗
PubMed1998

Preparation of a candidate primary reference material for the international standardisation of HbA1c determinations.

We prepared a candidate primary reference material for the forthcoming international standardisation of beta-N-terminal glycated hemoglobin A measurements. It consists of well-defined mixtures of purified beta-N-terminal glycated hemoglobin A and non-glycated hemoglobin A. First, beta-N-terminal glycated hemoglobin A and non-glycated hemoglobin A were isolated, purified to homogeneity, and characterised. The techniques used were cation exchange and affinity chromatography for the purification, and high performance liquid chromatography, capillary isoelectric focusing, electrospray ionisation mass spectrometry, and peptide mapping for the characterisation. Hemoglobins from blood of healthy, non-diabetic volunteers were obtained with a purity of > 99.5% for non-glycated hemoglobin A and of > 98.5% for beta-N-terminal glycated hemoglobin A. However, results from peptide mapping indicate that the beta-N-terminal glycated hemoglobin A preparations still contain some non-beta-N-terminal glycated hemoglobins, co-eluting with beta-N-terminal glycated hemoglobin A. The exact content of beta-N-terminal glycated hemoglobin A in these preparations could be determined by a procedure consisting of standard addition, enzymatic cleavage and quantification of the resulting beta-N-terminal peptides to be in the range from 95-97.5%. Since the beta-N-terminal glycated hemoglobin A and non-glycated hemoglobin A content could be exactly determined in the materials prepared, mixtures of both components could be successfully used to calibrate the candidate reference methods.

Chromatography, Affinity↗
PubMed1997

Two types of polyadenated mRNAs are synthesized from Drosophila replication-dependent histone genes.

The polyadenylation of replication-dependent histone H2B, H3 and H4 mRNAs in Drosophila melanogaster was analysed. Two types of mRNAs, containing a poly(A) tail, can be detected in addition to non-polyadenylated messengers, which represent the majority of replication-dependent histone mRNAs. Firstly, conventional polyadenylation signals, localized downstream from the stem-loop region, are used to produce polyadenylated mRNAs. The messengers of this type, generated from the D. melanogaster H2B gene, are preferentially synthesized in the testis of the fly. Secondly, a distinct type of polyadenylated histone mRNA has been identified. This mRNA, which is present in many different tissues and constitutes a minor part of the total histone mRNA pool, contains a short poly(A) tail, added to the end of the 3' terminal stem-loop structure, which is in most cases lacking several nucleotides from its 3' end. The sites of polyadenylation within the stem-loop are not preceded by a normal polyadenylation signal. The possible functions of the polyadenylated histone transcripts are discussed.

Animals↗
PubMed1997

Myosin rod protein: a novel thick filament component of Drosophila muscle.

Myosin rod protein (MRP), a 155 kDa protein encoded by a gene internal to the Drosophila muscle myosin heavy chain (Mhc) gene, contains the MHC rod domain, but has 77 unique N-terminal residues that exactly replace the MHC motor and light chain binding domains. Originally described as an abundant testis protein, we now demonstrate the MRP also is a major component of myofilaments in Drosophila. Specifically, the Mrp promoter directs the expression of a LacZ reporter transgene in somatic, cardiac and visceral muscles. MRP-specific antibodies detect the protein in detergent-insoluble fractions of muscle extracts and co-localize the protein with MHC to the sarcomeric A-band in immunostained muscles. Immunoblot analysis shows that in a set of adult direct flight muscles (DFM), the ratio of MRP to MHC is 1:3. Chemical cross-link and co-immunoprecipitation experiments using 0.5 M KCl-extracted thick filament proteins indicate that native MRP is a homodimer. Electron microscopy of DFM49, which has a high MRP content, shows in cross section, disordered myofilament packing and a variable thin to thick filament ratio and, in longitudinal section, severely bent thin filaments that are not well associated with thick filaments. In rigor, thick filaments from DFM49 consist of segments with cross bridges that are interspersed with smooth domains lacking cross bridges. These data indicate that MRP is a novel contractile protein that co-integrates with myosin into the thick filament, thereby changing structure and function of the sarcomere.

Amino Acid Sequence↗
PubMed1997

Naturally occurring testis-specific histone H3 antisense transcripts in Drosophila.

While analysing the transcription of the cluster of cell-cycle regulated histone genes in Drosophila hydei, we have found transcripts spanned both histone H3 and H4 genes and were antisense for histone H3. As the two histone genes are in opposite orientation, these transcripts contained the sense strand of the histone H4 gene. Such transcripts were present in both poly(A)+ and poly(A)- RNA fractions. The polyadenylated molecules contained a poly(A) tail at the 3' end of the stem-loop structure, which is characteristic for cell-cycle regulated histone mRNAs. The antisense RNA of histone H3 is synthesized exclusively in testes. By developing an improved protocol of in situ hybridization to Drosophila testis squashes, we could demonstrate that the antisense transcripts are localized in the nuclei of primary spermatocytes. Possible functions of this RNA are discussed.

Animals↗
PubMed1997

The localization of histone H3.3 in germ line chromatin of Drosophila males as established with a histone H3.3-specific antiserum.

A rabbit antiserum, specific for the histone H3.3 replacement variant, was raised with the aid of a histone H3.3-specific peptide. Immuno blot experiments demonstrated the specificity of this polyclonal antiserum. In addition, we showed on immuno blots that two monoclonal antibodies isolated from mice with systemic lupus erythematosus (SLE) display strong reactivity with the H3.3 histone, but not with its replication-dependent counterparts. Our observations indicate that histone H3.3 might play a role as autoantigen in SLE. We used the histone H3.3-specific antiserum to characterize the germ line chromatin in cytological preparations of Drosophila testes, because our previous studies had shown that a histone H3.3-encoding gene is strongly expressed in the germ line of Drosophila males. The antiserum reacted with some of the lampbrush loops in spermatocytes and with chromatin of the postmeiotic germ cells of males. Our data indicate that histone H3.3 is not evenly distributed throughout the chromatin of germ cells, but is concentrated in distinct regions. Histone H3.3 disappears from the spermatid nuclei, along with the other core histones, during the late stages of spermatogenesis. In Drosophila polytene chromosomes, however, a rather uniform distribution of the histone H3.3 was observed. The possible role of histone H3.3 is discussed.

Amino Acid Sequence↗
PubMed1997

Evaluation of the Menarini-Arkray HA 8140 hemoglobin A1c analyzer.

We describe a multinational evaluation of the Menarini-Arkray HA 8140 hemoglobin (Hb) A1c analyzer, which utilizes a high degree of automation, including bar code reading, cap piercing, and whole-blood sampling. With-in- and between-batch CVs were < 2%. Linearity was confirmed throughout the working range of the analyzer. Common Hb variants, including Hb S, Hb C, and Hb F, did not interfere with the Hb A1c separation, and the potentially interfering labile Schiff base was effectively removed during the chromatographic procedure. The HA 8140 analyzer displayed good correlation to the Bio-Rad Variant analyzer, Tinaquant immunoassay, affinity chromatography, and an optimized "in-house" HPLC Hb A1c method. The methods when compared by Altman and Bland plots showed bias (upper, lower 95% confidence limits) of: Variant minus HA 8140 = 0.99 (0.23, 1.74), Tinaquant minus HA 8140 = 0.14 (-0.71, 0.98); affinity minus HA 8140 (after log transformation) = 1.13 (0.90, 1.41), and "in house" HPLC minus HA 8140 (after log transformation) = 0.91 (0.82, 1.01).

Anticoagulants↗
PubMed1997

Candidate reference methods for hemoglobin A1c based on peptide mapping.

A reference method that specifically measures hemoglobin (Hb) A1c is an essential part of the reference system for the international standardization of Hb A1c/glycohemoglobin. We have developed a new method for quantification, based on the specific N-terminal residue of the hemoglobin beta-chains. Enzymatic cleavage of the intact hemoglobin molecule with endoproteinase Glu-C has been optimized to obtain the beta-N-terminal hexapeptides of Hb A1c and Hb A0. These peptides have been separated by reversed-phase HPLC and quantitated by electrospray ionization-mass spectrometry (method A) or by capillary electrophoresis (method B). With these peptides and hyphenated separation techniques, it has been possible to overcome the insufficient resolution of currently used protein separation systems for Hb A1c.

Chromatography, High Pressure Liquid↗
PubMed1996

Identification and characterization of the Drosophila histone H4 replacement gene.

Replacement variant genes for different histones have been described in most higher eukaryotes. However, so far no such gene has been found for histone H4. We have isolated from both Drosophila melanogaster and D. hydei a novel histone H4 encoding gene, H4r, which displays all the properties of a histone replacement variant gene: it contains introns, generates polyadenylated mRNA, represents the predominant H4 transcript in non-dividing tissues and is present in the genome as a single copy. The encoded polypeptide is identical to the Drosophila cell-cycle regulated histone H4. The fact that it is a single copy gene makes it prone to genetic analysis and it might be a useful tool for studying nucleosome structure and function.

Amino Acid Sequence↗