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T Haghfelt

Publications and source records attributed to T Haghfelt.

At least 19 recordsLinked to original sources
PubMed1996

Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods. METHODS: The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years). RESULTS: The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups. CONCLUSION: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent.

Adult↗
PubMed1996

Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study.

BACKGROUND: Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% (P=.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths (P=.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences, P<.0001). The corresponding number of hospital days was 15089 and 9951 in the two groups, respectively (34% reduction,P<.0001). In the United States, the resulting reduction in hospitalization costs over the 5.4 years of the trial would be $3872 per patient, reducing the effective cost of simvastatin by 88% to $0.28 per day. CONCLUSIONS: In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.

Adult↗
PubMed1996

Active compression-decompression cardiopulmonary resuscitation--instructor and student manual for teaching and training. Part I: The workshop.

In an attempt to standardize the teaching and training of active compression-decompression cardiopulmonary resuscitation (ACD-CPR), a group of leading emergency physicians, cardiologists, anesthesiologists, paramedics and nurses with practical, theoretical, educational, and scientific experience in the subject met in June 1995. The group was called The International Working Group of Teaching and Training Active Compression-Decompression CPR. The group was 'born' as a result of the first International Conference of Active Compression-Decompression CPR held in Copenhagen in March 1995. The following paper describes the background, development and text of and ACD-CPR course manual for both students and instructors.

Cardiopulmonary Resuscitation↗
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↗
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

Thrombolysis in acute myocardial infarction. The implementation of thrombolytic therapy in a coronary care unit in 1992.

In order to describe the execution of thrombolytic therapy in acute myocardial infarction (AMI) in a coronary care unit, case records of 427 admissions in 1992 due to definite or possible AMI were reviewed: 32% received thrombolytic therapy while 68% did not because of contraindications, delayed admission, advanced age or nondiagnostic ECG changes. Among cases otherwise eligible for thrombolytic therapy according to the instructions of the department, 32% did not receive thrombolytic treatment solely because of nondiagnostic ECG changes. There is an obvious need for implementation of improved early diagnostic tools in the decision-making of thrombolysis as for instance newer, sensitive biochemical markers and continuous vectocardiography.

Adult↗
PubMed1993

[Optimal treatment of chronic heart failure--with particular emphasis on angiotensin-converting enzyme (ACE) inhibitors].

The article reviews recent discoveries about the pathophysiology of chronic heart failure, especially where new insights have led to new treatment strategies, with particular emphasis on the use of angiotensin converting enzyme inhibitors. Indications for referral of patients with chronic heart failure to hospital for further investigation or treatment are also given. It is concluded that ACE-inhibitors represent a new era in the treatment of chronic heart failure in patients with isolated or for the main part systolic left ventricle dysfunction, and that ACE-inhibitor treatment must be regarded as a first line drug in this condition, along with diuretics and perhaps digoxin. Patients in NYHA class IIIb-IV should be referred to a specialist or hospital with regard to supplemental cardiological investigations and initiation of ACE-inhibitor treatment, if such treatment has not already ben started. Patients with slight to moderate heart failure (NYHA class II-IIIa) should be referred as well, unless it is known that the cause of heart failure is an ischaemic heart condition that does not require operation. In the latter case, after the relevant investigations have been conducted, ACE-inhibitor treatment can usually be started in a general practice setting, bearing the usual safety regulations and contraindications in mind.

Adult↗
PubMed1993

[Treatment of primary hypercholesterolemia with pravastatin. A placebo-controlled trial].

We present the results of a multicentre, placebo-controlled, randomized double-blind comparison of the treatment of primary hypercholesterolaemia with pravastatin (Pravachol), an HMG-CoA-reductase inhibitor. The study was conducted in both general practice and hospital settings. Two hundred and eighty-six patients who despite oral and written dietary instructions and advice on healthy living had elevated total serum cholesterol levels of between six and eight mmol/l were randomized to treatment with either parvastatin (Pravachol) or placebo. The study showed a significant reduction in both total serum cholesterol (of 16%) and serum LDL-cholesterol among those treated with pravastatin (Pravachol), as well as a small increase tin serum HDL-cholesterol of six percent. Advice on diet and healthy living resulted in a reduction of serum cholesterol of only 1.5%. There were no important differences between those treated from the hospital and those treated in general practice. The incidence of side-effects was low and comparable to placebo levels, and only two percent of the pravastatin (Pravachol) treated patients had to have the treatment stopped. All side-effects were reversible. No side-effects relating to the central nervous system were registered, and no elevations of serum creatinine phosphokinase were observed amongst the pravastatin treated patients, presumably because of the drug's selective inhibitory effect on cholesterol synthesis in the liver.

Adult↗
PubMed1993

[Neurohormonal activity in heart insufficiency].

The maintenance of cardiac pumping ability in the presence of a primary disturbance of myocardial contractility and/or an excessive haemodynamic strain on the heart is dependent on several compensatory mechanisms. Particular attention has formerly been paid to the importance of the Frank-Starling mechanism and cardiac hypertrophy and dilatation in maintaining a blood supply sufficient to cover the metabolic needs of various tissues in heart failure. In recent years, however, it has been found that certain neurohormonal systems (the sympathetic nervous system, the renin-angiotensin-aldosterone system, atrial natriuretic peptide and several locally acting vaso-active substances) undergo considerable changes according to the degree of heart failure. These compensatory mechanisms support the circulation wholly or partially in acute heart failure, however sustained neurohormonal activation may be harmful in chronic heart failure, where several neurohormonal factors may be activated to ill-effect. The most significant neurohormonal systems and their importance in heart failure are reviewed on the basis of the available literature.

Atrial Natriuretic Factor↗