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Biomedical subjects

M L Larsen

Publications and source records attributed to M L Larsen.

At least 19 recordsLinked to original sources
PubMed2006

Forearm plethysmography in the assessment of vascular tone and resistance vasculature design: new methodological insights.

AIM: High peripheral resistance and structural alteration in resistance arteries are central phenomena in essential hypertension and have been widely examined by forearm venous occlusion plethysmography; at rest for studying vascular tone, and during reactive hyperaemia for studying vascular structure. This work concerns the influence of venous pressure on hyperaemic vascular resistance (Rmin), the reproducibility of hyperaemic and resting vascular resistances (Rrest) and the relation between forearm and total peripheral vascular resistance (TPR). METHODS: In four healthy subjects, intravenous and intra-arterial blood pressures were measured simultaneously with plethysmographic recordings of hyperaemic and resting forearm blood flows. Reproducibility was examined in 15 young and 14 middle-aged healthy subjects and in 21 untreated hypertensive patients. RESULTS: Rmin remained low in the first recorded cardiac cycle, but rose in the second, even though corrected for the venous pressure rise, suggesting vascular tone recovery along with venous congestion. Between-day reproducibility of Rmin was high in middle-aged normotensive (8.7%) and hypertensive subjects (10.6%), but Rmin fell significantly between successive days in the young subjects. Rrest correlated with TPR, but required up to 40 min to reach steady state and showed high day-to-day variation in young (21.8%) and hypertensive subjects (16.2%). CONCLUSIONS: During hyperaemia, vascular resistance should be measured in the first cardiac cycle following venous occlusion to minimize influences of venous pressure rise and possible tone recovery. Rrest seems to reflect TPR. About 20 subjects may be needed to detect 15% changes between days in Rrest, fewer when concerning Rmin and TPR.

Adult↗
PubMed2006

Danish singles have a twofold risk of acute coronary syndrome: data from a cohort of 138 290 persons.

STUDY OBJECTIVE: Atherosclerosis of the coronary and other arteries is an important health problem in virtually all countries of the world, and thus there is a persisting need for the development of preventive programmes including population risk group identification. The aim of the study was to identify sociodemographic population risk indicators of an initial episode of acute coronary syndrome (ACS), including unstable angina pectoris (UAP), myocardial infarction (MI), and sudden cardiac death (SCD). DESIGN: Cohort study of 138 290 residents of the municipality of Aarhus, Denmark, aged 30-69 years. Information on population members' individual age, sex, social background, and eventual death was obtained from Danish Population Registers. SETTING: University hospital. PATIENTS: The study prospectively identified 646 victims of ACS from 1 April 2000 to 31 March 2002. MAIN RESULTS: Based on multiple logistic regression, age and single living were found to be positively associated with incident ACS in both sexes. Women >60 years living alone and men >50 years living alone were at especially high risk. They constituted only 5.4% and 7.7% of the source population, respectively, but they accounted for 34.3% and 62.4% of ACS patients dying within 30 days. CONCLUSIONS: Single living is associated with an increased risk of ACS. Thus, risk groups identified by use of information on their age and family structure may be targets for future more focused and cost effective preventive strategies. In Western populations, such high risk groups will constitute comparatively limited parts of the population, and in Denmark they are easily identifiable in routine population registers.

Acute Disease↗
PubMed2005

Repulsive synchronization in an array of phase oscillators.

We study the dynamics of a repulsively coupled array of phase oscillators. For an array of globally coupled identical oscillators, repulsive coupling results in a family of synchronized regimes characterized by zero mean field. If the number of oscillators is sufficiently large, phase locking among oscillators is destroyed, independently of the coupling strength, when the oscillators' natural frequencies are not the same. In locally coupled networks, however, phase locking occurs even for nonidentical oscillators when the coupling strength is sufficiently strong.

Journal Article↗
PubMed2004

Quality of lipid-lowering therapy in patients with ischaemic heart disease: a register-based study in 3477 patients.

OBJECTIVE: To develop a method to evaluate routine management practices concerning lipid-lowering treatment in patients with ischaemic heart disease (IHD) in a large geographic area. DESIGN: A register-based study linking information on IHD with cholesterol levels and prescriptions on lipid-lowering medications by personal registration number. Plasma cholesterol levels were collected from the electronic laboratory information system (LIS), and information on IHD from the Danish National Hospital Register (LPR). The extent of treatment was evaluated by information on prescriptions on lipid-lowering medications from the Danish National Health Service. SETTING: Evaluates treatment in both hospitals and primary care. SUBJECTS: Patients with IHD. RESULTS: In total 3477 patients <75 years were identified, and 43.7% had claimed prescriptions on lipid-lowering medications (01.01.2000-31.07.2000). In the whole population, 42% reached the goal for total cholesterol lower than 5 mmol L-1 set by European guidelines. In the 1521 patients treated with lipid-lowering medications 55% reached the goal. CONCLUSION: By use of registers it was possible to develop a method to evaluate and monitor current treatment practice for dyslipidaemia in a large geographic area. The method makes it possible to evaluate the impact of guidelines, changes in treatment procedures and to provide feedback to physicians. The study revealed that lipid-lowering treatment is still not sufficiently implemented in clinical practice even in patients with known IHD, and the used doses of statins are lower than those used in randomized clinical trials.

Aged↗
PubMed2002

Statins decrease bone turnover in postmenopausal women: a cross-sectional study.

BACKGROUND: Statins have been suggested as potential agents in the management of osteoporosis. Reviews of medical records have shown an increased bone mass and some studies have shown a reduced occurrence of fractures in subjects on long-term treatment with statins. We studied the effects of treatment with statins on calcium homeostasis, bone turnover and bone mineral density. DESIGN: In a cross-sectional design, plasma levels of parathyroid hormone (PTH) and biochemical markers of bone turnover, bone mineral density (BMD) and body composition (fat- and lean tissue-mass) were measured in 140 postmenopausal women who had been treated with a statin for more than 2 years (median 4 years) and compared to 140 age- and gender-matched, population-based controls. RESULTS: Plasma levels of bone turnover markers were lower in the statin-treated subjects than in the controls: osteocalcin (-9%, P = 0.03), bone-specific alkaline phosphatase (-14%, P < 0.01), and C-terminal telopeptide of type I collagen (-11%, P < 0.01). On the other hand, plasma PTH levels were 16% higher in the statin-treated subjects than in the controls (P < 0.01). However, body composition and BMD at the lumbar spine, hip, forearm and whole body did not differ between the two groups. No correlation could be demonstrated between changes in biochemical quantities and dose or duration of statin use. CONCLUSION: Our data show that statins affect the function of bone cells. Most likely, the effect is antiresorptive.

Aged↗
PubMed2001

[Examination and treatment of dyslipemia after myocardial infarction--are the goals achieved?].

According to guidelines, medical treatment of dyslipidaemia in post-AMI patients should await assessment of underlying lipid disorders and the outcome of dietary treatment. The risk of patients not being treated with lipid-lowering therapy because of lack of follow-up has led to more aggressive guidelines recommending statin treatment even before discharge from hospital. In a study comprising 730 patients, we have shown that, although most patients were discharged from the coronary care unit without statin treatment, a traditional rehabilitation programme succeeded in assessing more than 95% of the patients for underlying lipid disorders, and more than 75% of patients with plasma cholesterol > or = 5.5 mmol/l received lipid-lowering therapy within the first year. Most patients were treated with statins. Statins, however, were given in smaller doses than those used in the clinical trials, and only 52% of the treated patients reached the recommended goal of plasma cholesterol lower than 5 mmol/l.

Adult↗
PubMed2000

Willingness to pay for arthritis symptom alleviation. Comparison of closed-ended questions with and without follow-up.

OBJECTIVE: To compare two methods of measuring willingness to pay (WTP): closed-ended questions with and without follow-up. METHODS: A measurement experiment based on dichotomous choice contingent valuation survey data is reported. Marginal WTP estimates for alleviation of rheumatoid arthritis symptoms resulting from treatment with a novel anti-rheumatic agent, cA2 (TNF-alpha blockade), were calculated. Monte Carlo simulations were undertaken to evaluate the methods with respect to their statistical power. RESULTS: The estimated marginal WTP values using closed-ended questions with and without follow-up were DKK 637 (US $91) and DKK 1,268 (US $181), respectively. A Wilcoxon's signed-rank test showed that the difference of DKK 631 was significant. Moreover, including a follow-up question increases the precision of the result. Monte Carlo simulations showed that trade-offs between power (i.e., the probability of a correct rejection of a false null hypothesis), efficiency, and size may exist in the two models. CONCLUSIONS: There was a significant difference between the WTP estimates when using closed-ended questions with and without follow-up. When choosing between the models, however, power, efficiency, and size could be used as selection criteria.

Adult↗
PubMed1999

Normolipidemia and hypercholesterolemia in persons heterozygous for the same 1592 + 5G --> A splice site mutation in the low-density lipoprotein receptor gene.

In the present study, we have characterized a unique splice donor G to A substitution in the moderately conserved + 5 position in intron 10 of the low-density lipoprotein (LDL) receptor gene. In two Danish families, carriers of the 1592 + 5G --> A mutation display a clinical phenotype ranging from healthy normocholesterolemic persons to classical heterozygous familial hypercholesterolemia (FH) patients. Reverse transcription-polymerase chain reaction (RT-PCR) of RNA from Epstein Barr virus (EBV)-transformed lymphoblasts obtained from members of both families demonstrated abnormal splicing generating two aberrant mRNAs due to either alternative splicing and skipping of exon 10 or activation of a cryptic splice site in intron 10 inserting 66 intronic base pairs. These abnormally spliced mRNAs were predicted to encode two abnormal receptor proteins containing an in-frame deletion of 75 amino acids and an insertion of 22 novel amino acids, respectively. Results obtained by immunofluorescence staining, flow cytometry, and confocal microscopy of transfected Chang and COS-7 cells expressing normal and mutant LDL receptors were compatible with nearly complete retention of the mutant proteins in the endoplasmic reticulum. Quantitative measurements of LDL receptor mRNAs from EBV-transformed lymphoblasts, however, did not reveal any significant differences in variant mRNA contents between mutation carriers in the families that could be related to degree of hypercholesterolemia.

Adult↗
PubMed1997

The clinical usefulness of glucated haemoglobin in diabetes care evaluated by use of a medical technology assessment strategy.

With the introduction of measurements of glycated haemoglobin in a single blood sample as an index of long-term blood glucose control, the clinically usefulness of these measurements was questioned. The aim of this study was to evaluate measurements of glycated haemoglobin as a new test for metabolic regulation in diabetes management by use of a medical technology assessment strategy. Technology assessment in medicine has been defined as "the art and science of evaluating medical practices", but the strategy has to be adjusted to the medical technology in question always including the following three stages: (a) problem definition and identification of medical technology, (b) analysis by testing the technology with consideration to its benefit and harm, its costs, and its social consequences, and (c) synthesis of the accumulated knowledge about the technology. Based on the out-put from the problem definition we found it necessary to investigate some of the identified problems ourselves before implementation of routine measurements of glycated haemoglobin. Several studies were accomplished to validate the laboratory technology in terms of analytical reliability and its clinical usefulness. We wanted to (1) define goals of analytical quality of assays of glycated haemoglobin based on clinical goals, (2) establish a laboratory method for measurements of glycated haemoglobin fulfilling the defined goals, (3) investigate the ability of measurements of glycated haemoglobin to characterize impaired glucose tolerance, (4) evaluate the clinical usefulness of measurements of glycated haemoglobin in the assessment of metabolic regulation in non-insulin-dependent diabetes mellitus (NIDDM), (5) compare physicians' assessment of metabolic control in insulin-dependent diabetes mellitus (IDDM) with measurements of glycated haemoglobin and determine whether knowledge of glycated haemoglobin values would result in improved metabolic control, and (6) evaluate the organizational and economical consequences of introducing regular measurements of glycated haemoglobin. The analysis required a multi-disciplinary approach. Based on our own studies and the available data information we found that measurements of glycated haemoglobin should be regarded the most clinically appropriate test of long-term glycemia and should be introduced into routine management of adult patients with IDDM and NIDDM with the following guidelines concerning methodologies, clinical utility, organizational consequences. The individual laboratory has to establish and secure its own method since at present we are still without an internationally accepted reference method or reference material. The method should measure HbA1c without measuring the labile intermediate pre-HbA1c and provide separate detection of haemoglobin variants. We investigated the analytical goals for the performance characteristics of assays based on biological variation and on the clinical significance of a certain change in concentrations in the individual. Different strategies lead to different analytical goals of CVA between 2-4%. An oral glucose tolerance test is still required to establish the diagnosis of diabetes. Measurements of glycated haemoglobin have been suggested as an alternative but a considerable overlap between the WHO-defined groups of normal and impaired glucose tolerance was observed. In patients with IDDM our studies demonstrated the limitations of traditional clinical judgement and the laboratory procedures in providing an accurate assessment of blood glucose control and that knowledge of HbA1c values allowed the clinician to identify patients in poor glycemic control and lead to improvement in glycemic control. In patients with NIDDM our study showed that measurements of HbA1c provided information that was otherwise not obtainable in the usual clinical setting in primary health care. Measurements of glycated haemoglobin were easily accepted by patients with diabetes. (ABSTRACT TRUNCA

Adult↗
PubMed1996

Phenotypic presentation of the FH-Cincinnati type 5 low density lipoprotein receptor mutation.

Familial hypercholesterolaemia (FH) is an autosomal dominant hereditary disease of lipid metabolism that in most families is caused by mutations in the low density lipoprotein receptor (LDLR) gene. Though more than 150 mutations are known, the clinical picture associated with most of these is not known. Genetic FH diagnosis may soon become routine in the setting of genetic counselling, and therefore thorough information on the phenotype-genotype relationship of different mutations is now important. In this study, index patients from each of 14 Danish FH families were screened for mutations in exon 2 of the LDLR gene using a denaturing gradient gel electrophoresis (DGGE)-based mutation screening assay. A deviating DGGE pattern identified two index patients, where subsequent sequencing revealed heterozygosity for the FH Cincinnati type 5 Trp23-to-Stop LDLR mutation. Data from three generations of the families allowed the first clinical and biochemical description of this mutation. Evidence that genetic analysis adds independent diagnostic information compared to traditional clinical/biochemical FH diagnosis was documented by demonstrating the presence of the FH Cincinnati mutation in a family member with a completely normal lipid profile. By comparison to non-FH family members, it was documented that carrier status for the FH Cincinnati mutation is associated with a significant risk of cardiovascular disease. Thus, genetic analysis may improve diagnostic precision and help to define more precisely which of the members of FH families are in need of preventive interventions and may aid in establishing phenotype-genotype relationships allowing more refined genetic counselling in FH.

Base Sequence↗
PubMed1995

Genetic diagnosis with the denaturing gradient gel electrophoresis technique improves diagnostic precision in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder of lipid metabolism caused by mutations in the LDL receptor gene. FH is characterized clinically by elevated LDL cholesterol level and premature coronary disease. Diagnosing FH on clinical grounds may be difficult, and previous genetic methods are too cumbersome for routine use except in the few populations with FH-founder mutations. A simple mutation screening technique based on denaturing gradient gel electrophoresis (DGGE) has been highly useful in detecting mutations in other genes, and in the present study we evaluated the diagnostic potential of this method for the diagnosis of FH. METHODS AND RESULTS: Conditions for screening exon 3 of the LDL receptor gene using the DGGE technique were established and 14 Danish FH families were examined. An index patient from 1 family had an abnormal DGGE pattern; consequently, an examination of exon 3 of the LDL receptor gene in 21 members of this patient's family was done. The DGGE pattern was seen only in patients with a definite clinical diagnosis of FH. Subsequent sequencing of exon 3 of the LDL receptor gene in these individuals revealed the presence of the French-Canadian type 4 Trp66-Gly mutation. However, in 4 of 11 cases in which a definite clinical diagnosis of FH had been made, the inheritance of the French-Canadian type 4 mutation could be rejected on the basis of genetic analysis. CONCLUSIONS: Introduction of a simple genetic analysis based on DGGE may improve the precision of diagnosis in FH families.

Adolescent↗
PubMed1995

[The Scandinavian Simvastatin Survival Study: the clinical consequences].

In the recently reported Scandinavian Simvastatin Survival Study (4S), 4,444 men and women between 35 and 70 years of age who had coronary heart disease and plasma total cholesterol concentrations of 212 to 310 mg per deciliter (5.5 to 8.0 mmol/l) received simvastatin or placebo for 5.4 years; in the treatment group, mortality from coronary heart disease was 42 percent lower and mortality from all causes was 30 percent lower. Further analysis of the relation between the risk of major coronary events and baseline cholesterol levels in patients randomised to placebo or simvastatin therapy in the study showed that simvastatin significantly reduced the risk of major coronary events in all quartiles of baseline total, high-density-lipoprotein, and low-density-lipoprotein cholesterol, by a similar amount in each quartile. Clearly, cholesterol-modifying interventions can substantially improve the outlook for patients with coronary heart disease and should be considered in identification and treatment of patients with established coronary heart disease. The available data from secondary intervention trials indicates that all patients with documented ischemic heart disease should be offered a reliable assessment of plasma total cholesterol. However, since the impact of simvastatin on CHD seems to begin after about one year of therapy it would be reasonable to exclude very old persons and patients with serious disease with a limited life-expectancy. As a consequence of the 4S data it should be recommended that all the patients in question, who after lifestyle modifications and non-pharmacological risk factor modification still have total cholesterol levels above 200 mg per deciliter (5.2 mmol) should be offered treatment with a HMG-CoA reductase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Detection of a single base deletion in codon 424 of the low density lipoprotein receptor gene in a Danish family with familial hypercholesterolemia.

We performed a screening of exon 9 of the low density lipoprotein receptor (LDLR) gene in 14 Danish families with familial hypercholesterolemia (FH) using the denaturing gradient gel electrophoresis (DGGE) technique. In one of the probands from these families an abnormal band pattern in the gradient gel was detected. Subsequent DGGE analysis of the family of this index patient revealed that the DGGE pattern cosegregated with the disease in this family. Sequencing of the exon showed a deletion of a C in codon 424 of the LDLR gene resulting in a frame shift with the introduction of a stop codon 5 codons further downstream. The mutation is referred to as FH-Odense. The predicted truncated receptor protein consists of the 428 amino terminal amino acids. Consequently, the cytosolic and membrane spanning parts of the mature LDL receptor, which normally secure the receptor in the plasma membrane, are missing. The FH-Odense mutation results in severe premature coronary atherosclerosis as shown by the clinical expression in 5 generations of the affected family.

Adolescent↗
PubMed1994

Comparative effects of gemfibrozil and clofibrate in type III hyperlipoproteinemia.

Type III hyperlipoproteinemia (dysbetalipoproteinemia) is characterized by elevated concentrations of plasma cholesterol and triglycerides due to an increase in very low density lipoprotein (VLDL) remnant lipoproteins. In a retrospective analysis we observed that in 12 patients with this disorder, gemfibrozil reduced concentrations of total cholesterol, VLDL cholesterol and triglycerides by 48%, 72% and 68%, respectively. These changes were greater than those reported in a similar number of patients treated with clofibrate. Comparative data on the efficacy of different fibrates in this disorder are very limited; to assess this further we have compared the hypolipidemic effects of gemfibrozil (600 mg twice daily) and clofibrate (1 g twice daily) in six patients with well-characterized type III hyperlipoproteinemia. Baseline values were obtained after at least 8 weeks on diet and treatment values were obtained after 6 and 8 weeks of treatment with each drug. Treatment with clofibrate and gemfibrozil both resulted in significant reductions in the plasma concentrations of total cholesterol (40% and 54%), VLDL cholesterol (59% and 79%) and total triglycerides (48% and 70%), as well as a significant increase in HDL cholesterol (9% and 7%). Gemfibrozil was, however, significantly (P < 0.05) more effective in reducing plasma concentrations of total cholesterol, VLDL cholesterol and triglycerides than was clofibrate, in the same patients.

Adult↗