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Biomedical subjects

M Eriksson

Publications and source records attributed to M Eriksson.

At least 145 records · Page 8Linked to original sources
PubMed1998

Compliance with and efficacy of treatment with pravastatin and cholestyramine: a randomized study on lipid-lowering in primary care.

OBJECTIVES: Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and cholestyramine are effective in reducing cardiovascular morbidity both in primary and secondary prevention. Patient compliance is an important determinant of the outcome of therapy. This study was designed to compare compliance with tolerance and lipid-lowering effectiveness of pravastatin and/or cholestyramine in primary care. DESIGN: Nine hundred and eighty nine women and 1047 men were randomized to treatment at 100 primary-care centres in Sweden. After dietary intervention, an eligible patient was randomly assigned to one of four programs of daily treatment: group Q, 16 g cholestyramine, group QP, 8 g cholestyramine and 20 mg pravastatin, group P20, 20 mg pravastatin or group P40, 40 mg pravastatin. RESULTS: In group Q, group QP, group P20 and group P40 the reductions in low density lipoprotein (LDL)-cholesterol were 26%, 36%, 27% and 32%. The dose actually taken was 91-95% of the prescribed for the pravastatin treatment groups and 77-88% for the cholestyramine groups. In the pravastatin and cholestyramine groups 76-78% and 44-53%, respectively, completed the trial. Only 8-27% of the patients reached a serum cholesterol target level of 5.2 mmol L-1. There was no difference in lipid-lowering effect between women and men. CONCLUSION: Pravastatin alone is efficacious and compliance is high, independent of dose. Combined treatment with cholestyramine and pravastatin had a better cholesterol lowering effect (although not statistically significant) than 40 mg pravastatin. Despite this, only 8-27% of the patients actually reached a serum cholesterol level of 5.2 mmol L-1. No unexpected serious adverse events were detected in any of the treatment groups. As predicted, the gastrointestinal disturbances were more common on cholestyramine treatment. These two factors suggest that an increase in the dosage of the HMG-CoA reductase inhibitor may be appropriate. Results from other studies indicate that there also might be other positive effects of statin treatment beyond cholesterol lowering.

Adult↗
PubMed1998

Low frequency of the common Norwegian and Finnish LDL-receptor mutations in Swedish patients with familial hypercholesterolaemia.

OBJECTIVE: To evaluate the frequency of the common Finnish and Norwegian mutations in the low density lipoprotein (LDL) receptor gene in Swedish patients with familial hypercholesterolaemia (FH), and to start screening for other mutations in these patients. In contrast to the situation in Norway and Finland, where the frequency of common mutations causing the disease has been determined, very little about the mutation spectrum is known in Sweden. SETTINGS AND SUBJECTS: In total, 182 unrelated Swedish patients fulfilling clinical criteria for FH were investigated. Of these, 112 were identified at Huddinge University Hospital in Stockholm, and 70 at Sahlgren's Hospital in Göteborg. They were screened by single-strand conformation polymorphism (SSCP) for mutations in exons 3, 4, 6 and 9 of the LDL-receptor gene and by polymerase chain reaction (PCR) for the most common FH mutations occurring in Finland. and the prevailing mutation causing familial defective apolipoprotein B-100 (FDB). RESULTS: Mutations in the LDL receptor were identified in 25 of the 182 patients. Of these, 10 represented FH-Helsinki and one FH-North Karelia. Other mutations identified were FH-Svartor (four patients), FH-Elverum (one patient), FH-Padova (two patients), FH-Morocco (one patient) and FH-Algeria-1 (one patient). One patient was simultaneously positive for two mutations formerly described in Sweden: E256K (exon 6) and 1402T (exon 9). Another mutation caused replacement of one amino acid residue in exon 6 (C292Y). Two new mutations were found, both in exon 6: one nonsense mutation in the codon #275 for cysteine (FH-Huddinge, two patients), and one deletion of two base-pairs in the codon for leucine in position 254 (FH-Göteborg, one patient). The mutation for FDB was found in three patients. CONCLUSIONS: The mutation pattern in Swedish FH patients differs considerably from that in Finland and Norway. The two new mutations discovered will probably cause serious functional disturbances in the LDL-receptor function. Thus far, no predominant mutation was seen in Swedish FH-patients.

Adult↗
PubMed1998

Endotoxaemic liver injury in a porcine model--relation to tumour necrosis factor-alpha release and survival.

The effects of a continuous infusion of E. coli endotoxin on liver blood chemistry, plasma TNFalpha and blood pressure were evaluated in relation to survival in 18 anaesthetized pigs. The endotoxin infusion cause both unconjugated and conjugated bilirubin to increase (both p < 0.001), as compared to 6 saline-infused controls. Four pigs died during the endotoxin infusion. The plasma levels of TNFalpha of these 4 non-survivors were higher compared to TNFalpha of the 14 surviving endotoxaemic pigs (p < 0.05). The increase in plasma bilirubin of the non-survivors was less expressed (p < 0.05), and their arterial blood pressure and base excess deteriorated (both p < 0.001) compared to surviving endotoxaemic pigs. A decreased blood pressure explains both the reduced 'hepatic washout' of bilirubin and visceral ischaemia, reflected by the development of metabolic acidosis. This porcine model may be suitable for studying endotoxaemic liver injury.

Animals↗
PubMed1998

Impaired platelet function in endotoxemic pigs analyzed by flow cytometry.

Endotoxin or bacterial lipopolysaccharide (LPS) is a structural component of Gram-negative bacteria. It is believed to be the major pathogenic factor of Gram-negative sepsis, and may result in intravascular coagulation and in a shock syndrome that is characterized by thrombocytopenia, leucopenia, hypotension, fever, reduced delivery of oxygen, metabolic acidosis and ultimately death. We have previously shown that both endotoxemic pigs and patients with Gram-negative sepsis have elevated levels of platelet microvesicles in their blood, which indicates platelet activation. In this study, we have used flow cytometry and fluorescein-labeled chicken anti-human fibrinogen to evaluate the in vivo effect of endotoxin on platelet function in a porcine model. Endotoxin infusion in pigs caused impaired platelet function when platelets were stimulated with adenosine-diphosphate in vitro ( P < 0.001). We also found a similarly decreased platelet function in patients with Gram-negative sepsis. Since flow cytometry is a rapid method for determination of platelet function, this method may turn out to be a useful tool in clinical situations. Our results may contribute to our understanding of the bleeding problems that may occur in septic shock and in disseminated intravascular coagulation.

Journal Article↗
PubMed1998

Failure to achieve gene conversion with chimeric circular oligonucleotides: potentially misleading PCR artifacts observed.

Recently, a novel strategy for nucleotide exchange of target DNA using chimeric RNA/DNA oligonucleotides (CO) was reported. The CO can easily be transfected into cells, remain stable within the cells, and migrate to the nucleus. We have in this study used 42 similar constructs for targeting six different human and canine loci. A variety of cationic lipids, electroporation, and microinjection were used for transfection of the CO into lymphoblastoids, Huh7, HT 1080, and Jurkat cell lines, and canine primary fibroblasts and hepatocytes. However, no nucleotide exchange was detected in any of the targeted loci. Using PCR followed by restriction enzyme analysis, nucleotide exchange in approximately 2%-10% of the PCR products was observed during the first 3 days after transfection with CO-vWF-28S2 designed for repairing a mutation in the von Willebrand gene. Surprisingly, the observed exchange reverted after culturing the cells for a longer period of time (14 days). Furthermore, a positive indication of gene conversion (5%) was also obtained using an allele-specific PCR method for analysis of the PAI-1 gene. However, cloning of the PCR products revealed no nucleotide exchange. In our view, the most likely explanation is that the initial false positive result originates from a PCR artifact created by the CO itself. Our results imply that an independent method, that is, Southern blotting, must be used to verify an observed nucleotide exchange.

Animals↗
PubMed1998

Oral infections and dental factors in relation to oral cancer: a Swedish case--control study.

We investigated the role of oral infections, dentition and dental X-rays for oral cancer in a north Swedish population. This case-control study consisted of 410 cases with oral cancer for the period 1980-89 and 410 matched controls. All subjects received a mailed questionnaire. The response rates were 96% and 91% for cases and controls, respectively. The univariate analysis showed a statistically significant increased risk for oral cancer among individuals reporting problems with recurrent clinical oral infection (odds ratio (OR) 3.8). Separate analyses were made for groups with a clearly stated HSV-1 infection (OR 1.9) and highly suspected HSV-1 infection (OR 3.3) as reported by the subjects. Odds ratios were also calculated for infections in relation to tobacco and alcohol habits. For individuals reporting recurrent infection problems an increased risk was observed in every combination category. Dental factors such as different fillings, dentures and fixed prostheses showed no increased risks. Dental X-ray did not produce an increased OR either. A multivariate analysis suggested that the most important risk factors were oral infections followed by liquor consumption and active smoking.

Alcohol Drinking↗
PubMed1998

Retinyl palmitate injections reduce serum levels and effects of endotoxin on systemic haemodynamics and oxygen transport in the pig.

BACKGROUND: Retinyl palmitate [(RP) 230 IU.kg(-1)] modulates the circulatory and respiratory responses of a subsequent infusion of endotoxin in the pig. The aims of this study were: I. To determine if RP (2300 IU.kg(-1)) affects the serum endotoxin levels in this model. II. To evaluate the effect of this dose of RP on circulatory and respiratory variables in our porcine model. III. To investigate the levels of RP and neutrophil count in porcine endotoxaemia. METHODS: Ten anaesthetized pigs were randomly given 2300 IU.kg(-1) of RP or the solvent i.m. prior to the continuous i.v. infusion of E. coli endotoxin (10 microg.kg(-1).h(-1)). Another 4 sham animals were given either i.m. RP (n=2) or i.m. solvent (n=2) followed by an infusion of saline. Haemodynamics and oxygen extraction were monitored and samples taken for analysis of endotoxin, RP and blood cells. RESULTS: I. Endotoxin levels in serum were lower (P<0.001) in the RP-pretreated pigs. II. These animals had higher cardiac index (P<0.05), mean arterial pressure and left ventricular stroke work index (both P<0.001), and lower oxygen extraction (P<0.01). III. RP-Pre=pretreatment caused a paradoxical decrease in serum retinyl (P<0.001) and a more rapid restitution of neutrophil count (P<0.05). CONCLUSION: Pretreatment with RP (2300 IU.kg(-1)) counteracts the progressive increase in serum endotoxin levels in porcine endotoxaemia.

Animals↗
PubMed1998

Increased platelet microvesicle formation is associated with mortality in a porcine model of endotoxemia.

BACKGROUND: Gram-negative sepsis in humans and endotoxemia in pigs induce the formation of platelet microvesicles. These microvesicles are active in homeostasis and may thus contribute to the outcome in patients with activated coagulation and fibrinolysis. We decided to prospectively evaluate the effects of endotoxemia on microvesicle formation and some common physiologic variables against survival in a porcine model. METHODS: Nineteen included pigs were anesthetized, monitored and subjected to an infusion of E. coli endotoxin. Microvesicle formation was determined by flow cytometry. RESULTS: The formation of microvesicles was significantly increased in the 6 pigs that died during endotoxin exposure. This increased formation became significant from the 3rd hour of endotoxemia. Microvesicle formation did not increase in surviving endotoxemic pigs. Cardiac index, mean arterial blood pressure, base excess and systemic vascular resistance index were distinctly reduced in the animals that died as compared to those surviving the endotoxemic period. CONCLUSION: The increased formation of platelet microvesicles seems to be associated with poor prognosis in porcine endotoxemia. Since microvesicles are active in coagulation, they may contribute to the derangement of the coagulation system caused by endotoxemia. Different degrees of microvesicle formation may reflect inter-individual responses to a given challenge.

Acidosis↗
PubMed1998

Risk factors for neonatal sepsis in offspring of women with prelabor rupture of the membranes at 34-42 weeks.

One thousand three hundred eighty-five women with PROM (prelabor rupture of the membranes) participated in a prospective randomized study. Women with PROM were randomized to induction the following morning after PROM (early induction group) or induction two days later (late induction group). If contractions started within 2 hours after admission these women were included in the short latency group. All neonatal infections were classified as verified sepsis (positive culture) or clinical sepsis. The aim of the study was to compare the perinatal infectious outcome between the groups with different expectant managements in women with PROM and to study the association between demographic, intrapartum and postpartum variables and neonatal sepsis. In the short latency group one neonate had a proven sepsis while four neonates with proven sepsis were found in the early induction group. No proven sepsis was detected in the late induction group. Univariate analyses showed a significant association between clinical sepsis and: induction of labor (OR = 2.94, 95% CI 1.30-6.68), established labor 24.1-32 hours after ROM (OR = 5.89, 95% CI 1.68-20.63), established labor > 32 hours after ROM (OR = 4.59, 95% CI 1.52-13.87), time from ROM to delivery > 32 hours (OR = 5.07, 95% CI 1.40-18.39), cesarean section (OR = 11.03, 95% CI 4.10-29.68), chorioamnionitis before or during delivery (OR = 27.14, 95% CI 2.38-309.16), endometritis (OR = 18.08, 95% CI 1.82-179.87), CRP over 20 mg/l in the umbilical cord (OR = 17.12, 95% CI 5.68-52.12) and Apgar score < 7 after 1, 5 or 10 minutes. In a stepwise logistic regression analysis a significant association was found between clinical sepsis and cesarean section (OR = 10.08, 95% CI = 3.26-31.20), time from ROM to delivery > 32 h (OR = 3.74, 95% CI 1.62-8.62), gestational age 34-36 weeks (OR = 3.16, 95% CI 1.11-8.96) and parous women (OR = 2.41, 95% CI 1.04-5.57). In conclusion, this study indicates that that there was no difference in the incidence of neonatal infections between those with early and late induction. Clinical neonatal sepsis was associated with time from PROM to delivery over 32 hours, cesarean section, parous women and gestational age between 34 and 36 weeks.

Apgar Score↗
PubMed1998

L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study.

Monoamine precursors, neurotransmitters and their metabolites were studied in cerebrospinal fluid (CSF) obtained from nine newly diagnosed hypothyroid patients. Before treatment, the serum TSH correlated positively with the CSF concentrations of tyrosine and phenylalanine. During treatment, the levels of the precursors tryptophan, phenylalanine and tyrosine decreased significantly, as was also the case with dopamine and the noradrenaline metabolite 4-hydroxy-3-methoxyphenylglycol (HMPG), but not with serotonin, noradrenaline and the serotonin metabolite 5-hydroxyindoleacetic acid, nor the dopamine metabolites homovanilic acid and dihydroxyphenylacetic acid. The study provided some indication that the CSF levels of phenylalanine and tyrosine are related to thyroid function. Furthermore, we have found an indication that L-thyroxine treatment affects the CSF levels of the precursors as well as dopamine and HMPG. Our results support the notion that there is an interaction between thyroid function and CSF disposition of monoamine compounds.

Adult↗
PubMed1998

Agent Orange in war medicine: an aftermath myth.

Since the late 1970s several epidemiological studies have appeared linking exposure to phenoxy herbicides or chlorophenols to some malignant tumors. Most of these compounds are contaminated with dioxins and dibenzofurans; for example, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a contaminant of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a component of Agent Orange which was sprayed in Vietnam during the war. The results of some of the epidemiological studies on cancer risks associated with exposure to these compounds have been manipulated and misinterpreted, particularly by the Australian Royal Commission on the Use and Effects of Chemical Agents on Australian Personnel in Vietnam. Furthermore, a book on Australian war history entitled Medicine at War, commissioned by the Federal Government, reiterates several of these misinterpretations, despite available contrary evaluations from Australian and U.S. authorities. These remarkable and confusing circumstances in the scientific process are considered also in the light of the recent classification of TCDD as carcinogenic to humans, Group 1, by a Working Group at the International Agency for Research on Cancer in Lyon, France.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1998

Water-solid interactions. IV. Influence of moisture sorption on the compaction of film-coated particles.

The effect of moisture sorption on the compaction properties of model modified-release (MR) pellets coated with ethyl cellulose/hydroxypropylcellulose film has been studied for the MR pellets alone and in binary mixtures with microcrystalline cellulose, lactose alpha-monohydrate, or lactose 9% amorphous. The in vitro dissolution rate prior to and after compaction was used as an indirect method of evaluating the effect of exposing the MR pellets to a compaction force. Moisture sorption as well as the glass transition temperature (Tg) using differential scanning calorimetry (DSC) were determined as a function of humidity for cast film conditioned at different humidities using a climate test chamber. The compaction properties of lactose and microcrystalline cellulose were altered by the addition of MR pellets, resulting in a robust tablet mass and a tensile strength of the tablet masses that was less sensitive to moisture. The amount of moisture sorbed was found to have little influence on the formation of cracks or on the rupturing of film-coated MR pellets during compaction. This was probably a result of both the small depression in the Tg for the film system at increasing RH and the robustness of the film chosen. The results also showed that the volume reduction properties of the tableting excipients were of importance for reducing damage to the film coating. Lactose had a higher protective effect on the film-coated MR pellets compared to microcrystalline cellulose.

Adsorption↗
PubMed1998

Platelet activity in vivo in hyperlipoproteinemia--importance of combined hyperlipidemia.

Platelet hyperactivity in vitro is found in patients with isolated hypercholesterolemia. It is, however, less well established if platelet activity in vivo is enhanced, and if there are differences between various types of hyperlipoproteinemia. Platelet function in vivo was studied at rest and during mental stress in men with isolated hypercholesterolemia (phenotype IIa; n = 21) or combined hyperlipidemia (phenotype IIb; n = 29), and age-matched normolipidemic controls (n = 41). The urinary excretion of 11-dehydrothromboxane B2 was elevated in patients compared to controls (IIa, p <0.05; IIb, p <0.001), and higher in type IIb than in IIa patients (p <0.05). Platelet secretion, assessed as plasma beta-thromboglobulin levels, was higher in type IIb patients compared to controls (p <0.01) and type IIa patients (p <0.05) during mental stress. The urinary excretion of beta-thromboglobulin was also elevated in type IIb patients compared to controls (p <0.05). Platelet aggregability at rest, as measured by filtragometry ex vivo was, however, reduced in both patient groups compared to controls (p <0.05). No correlations were found between plasma lipoprotein levels and markers of platelet function in vivo. Type IIb patients had higher plasma fibrinogen levels and higher leukocyte counts than controls (p <0.05 and p <0.001) and type IIa patients (p <0.05 and p = 0.06). Thromboxane excretion was positively related to fibrinogen levels and leukocyte counts (p <0.01 for both). Preliminary data regarding serum TNF-alpha also indicated an elevation of this inflammatory cytokine in type IIb patients (p <0.05 vs controls). In conclusion, thromboxane generation and platelet secretion in vivo are enhanced in patients with hypercholesterolemia, and particularly so among patients with concomitant elevation of plasma triglycerides. The mechanism is unknown, but inflammatory mediators may be involved. The present findings are of interest in relation to the role of triglycerides in coronary artery disease.

Adult↗
PubMed1998

Melagatran, a low molecular weight thrombin inhibitor, counteracts endotoxin-induced haemodynamic and renal dysfunctions in the pig.

Coagulation and fibrinolysis are crucial in septic shock and inhibition of thrombin may be beneficial in this circumstance. Since porcine endotoxaemia has been found to replicate severe septic shock, a low molecular weight thrombin inhibitor, melagatran, was infused during the first 3 out of 6 h of endotoxaemia in pigs. Plasma creatinine (p <0.01) and urinary output (p <0.05) were less affected in the melagtran + endotoxin group (n=6) as compared to endotoxaemic controls (n=9). The left ventricular stroke work index, systemic vascular resistance index and oxygen extraction were all less affected (p <0.05) by endotoxin during the infusion of melagatran. The plasma concentration of melagatran declined with an apparent plasma half-life of 5 h as soon as the infusion was stopped. APTT, however, continued to increase after the infusion of melagatran had stopped and reached a maximum of 113 s at 5 h (baseline 17 s). APTT in endotoxaemic control pigs reached a maximum of 22 s. Thus, melagatran may counteract some consequences of endotoxaemia.

Animals↗
PubMed1997

A new mechanism-based radical intermediate in a mutant R1 protein affecting the catalytically essential Glu441 in Escherichia coli ribonucleotide reductase.

The invariant active site residue Glu441 in protein R1 of ribonucleotide reductase from Escherichia coli has been engineered to alanine, aspartic acid, and glutamic acid. Each mutant protein was structurally and enzymatically characterized. Glu441 contributes to substrate binding, and a carboxylate side chain at position 441 is essential for catalysis. The most intriguing results are the suicidal mechanism-based reaction intermediates observed when R1 E441Q is incubated with protein R2 and natural substrates (CDP and GDP). In a consecutive reaction sequence, we observe at least three clearly discernible steps: (i) a rapid decay (k1 >/= 1.2 s-1) of the catalytically essential tyrosyl radical of protein R2 concomitant with formation of an early transient radical intermediate species, (ii) a slower decay (k2 = 0.03 s-1) of the early intermediate concomitant with formation of another intermediate with a triplet EPR signal, and (iii) decay (k3 = 0.004 s-1) of the latter concomitant with formation of a characteristic substrate degradation product. The characteristics of the triplet EPR signal are compatible with a substrate radical intermediate (most likely localized at the 3'-position of the ribose moiety of the substrate nucleotide) postulated to occur in the wild type reaction mechanism as well.

Binding Sites↗
PubMed1997

Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease.

BACKGROUND: Hypertriglyceridemia is now accepted as a risk factor for coronary heart disease, although the mechanism behind the increased risk is not well understood. The present study was undertaken to investigate the effects of triglyceridemia on endothelial function, because impaired endothelial function is considered a marker of atherogenesis. METHODS AND RESULTS: Flow- and nitroglycerin-induced dilatation of the brachial artery was investigated noninvasively by high-resolution ultrasound technique in seven young, healthy men without risk factors for coronary heart disease. Transient triglyceridemia was induced by infusion of a triglyceride emulsion, Intralipid, which raised free fatty acid concentrations twofold and triglyceride levels fourfold. Flow-induced vasodilatation decreased from 7.1+/-3.0% to 1.6+/-2.6% (P<.0002), whereas nitroglycerin-induced vasodilatation decreased from 20.5+/-5.8% to 11.5+/-3.2% (P<.002) before and after 1 hour of infusion of Intralipid, respectively. CONCLUSIONS: Transient triglyceridemia decreases vascular reactivity, presumably by both endothelium-dependent and endothelium-independent mechanisms.

Adult↗