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Biomedical subjects

A Hedman

Publications and source records attributed to A Hedman.

At least 19 recordsLinked to original sources
PubMed2004

Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene.

We investigated inducibility of life-threatening arrhythmias with programmed ventricular stimulation (PVS) in relation to clinical markers of sudden cardiac death (SCD) in subjects with hypertrophic cardiomyopathy (HCM) attributable to the Asp175Asn mutation in the alpha-tropomyosin gene (TPM1-Asp175Asn). PVS was performed with up to three extrastimuli and distribution of markers of SCD was evaluated in 21 adult subjects with the TPM1-Asp175Asn. Sustained polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) was induced in seven of 21 subjects (33%). Inducible subjects had more severe left ventricular hypertrophy (LVH) and an increased number of markers of SCD (family history of SCD, syncope or presyncope, fall in systolic blood pressure (BP) during exercise, documented non-sustained VT (NSVT), and marked LVH) compared to non-inducible subjects (IVS 2.4 +/- 0.3 cm vs. 1.6 +/- 0.5 cm, P < 0.001; and two to three vs. one to two markers of SCD, P = 0.007, respectively). In conclusion, in HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, life-threatening arrhythmias were induced in one third of the patients. Inducibility was associated with the maximum left ventricular (LV) thickness and the number of markers of SCD, suggesting that in HCM patients with an identical causative mutation, susceptibility to ventricular arrhythmias is related to the cardiomyopathic phenotype.

Adult↗
PubMed2003

Cardiac arrest after interscalene brachial plexus block with ropivacaine and lidocaine.

Serious adverse reactions to ropivacaine and lidocaine are rare. In this report, we describe a case of sudden cardiac arrest after an interscalene brachial plexus block with a mixture of 150 mg of ropivacaine and 360 mg of lidocaine in a previously healthy, 34-year-old, 97-kg man. Severe hypotension occurred after successful resuscitation, necessitating an infusion of epinephrine. The patient developed pulmonary oedema, and was mechanically ventilated for 22 h. He eventually made a good recovery. We conclude that although ropivacaine and lidocaine are often considered relatively safe local anesthetics, serious cardiovascular complications can occur after the use of these drugs.

Adult↗
PubMed2002

Prediction of atrial fibrillation after coronary artery bypass grafting by measuring atrial peptide levels and preoperative atrial dimensions.

OBJECTIVE: We prospectively tested the hypothesis that atrial enlargement and increased level of atrial natriuretic peptide, N-terminal atrial natriuretic peptide and brain natriuretic peptide would predict atrial fibrillation after coronary artery bypass grafting. METHODS: Eighty-eight elective coronary artery bypass grafting patients had preoperative echocardiographic assessment. The level of atrial natriuretic peptide, N-terminal atrial natriuretic peptide and brain natriuretic peptide were measured preoperatively. Patients were ECG- monitored during the whole hospital stay. RESULTS: Thirty one (35.2%) patients had postoperative atrial fibrillation. In univariate analysis increased age (P=0.003), enlargement of left and right atria (P=0.002 and P=0.004, respectively) and increased level of preoperative atrial natriuretic peptide and N-terminal atrial natriuretic peptide (P=0.016 and P=0.03, respectively) were associated with postoperative atrial fibrillation. There was correlation between the age and level of N-terminal atrial natriuretic peptide (r=0.45 and P<0.001). In multivariate analysis only age and the left atrial enlargement were independent predictors of postoperative atrial fibrillation (P=0.02 and P=0.01). CONCLUSION: Left atrial enlargement was independent predictor for postoperative atrial fibrillation. However, atrial peptides were associated with age and did not independently predict postoperative atrial fibrillation. In addition, the wide variation of the peptide levels renders the implementation of this measure in clinical practice superfluous.

Age Factors↗
PubMed2002

Muscle morphology, self-reported physical activity and insulin resistance syndrome.

In a population-based sample of 475 men the associations between muscle morphology, self-reported physical activity (PA) and insulin resistance (IR) syndrome were investigated. Also, we studied to what degree muscle morphology contributes to the association between PA and IR syndrome. Muscle morphology and the components of IR syndrome were compared in four groups categorized according to self-reported habitual PA data. We found a significantly higher percentage of type I fibres, fibre area and number of capillaries around the fibres and a lower proportion of type IIB fibres with higher level of PA. The relative distribution of type I fibres and capillarization were positively related to high density lipoprotein (HDL) cholesterol and negatively to serum triglycerides (TG) and plasminogen activator inhibitor-1 (PAI-1) activity. The percentage of type IIB fibres was were inversely related to HDL cholesterol and positively to serum TG, PAI-1 activity and resting heart rate. Insulin sensitivity was positively and independently related to PA level (P < 0.001). Regression analysis including all relevant variables regarding insulin sensitivity indicated that the significant explanatory variables left in the equation were body mass index (BMI), glucose intolerance, PAI-1 activity, serum free fatty acid concentration, proportion of type IIB fibres, HDL cholesterol level, drug treatment, PA level, and waist-to-hip ratio, which together explained 55% of the variation in the insulin sensitivity index. In conclusion, both fibre type distribution and muscle capillary density might contribute to the beneficial effect of PA on IR syndrome.

Aged↗
PubMed2001

Insulin-mediated changes in leg blood flow are coupled to capillary density in skeletal muscle in healthy 70-year-old men.

The aim of this study was to investigate to what degree the capillarization in the skeletal muscle explains the leg blood flow (LBF) changes during hyperinsulinaemia. Fifteen normotensive men from a population-based cohort of 70-year-old men in Uppsala, Sweden, were investigated. Their metabolic status (oral glucose tolerance test and euglycemic, hyperinsulinaemic clamp test results), serum lipid profile, muscle fiber distribution (myosin adenosine triphosphatase staining), and capillary supply (amylase-periodic acid-Schiff method) was evaluated. Doppler ultrasound was used before and after the clamp test to detect insulin-induced changes in LBF. Physiologic hyperinsulinemia (serum insulin, 107 mU/L) caused a moderate increase in LBF (15% +/- 11%; P =.07). Change in LBF was closely related to capillary density (r =.66; P <.01) independent of obesity, smoking and level of physical activity. An association was observed between LBF and serum free fatty acid (FFA) concentrations (r = -.57; P <.05). In multiple regression analysis, capillary density and serum FFA level together explained 71% of the variation in insulin-mediated LBF changes. Capillary rarefaction and elevated serum FFA values were associated with a vasoconstrictive effect of insulin. In conclusion, capillarization in skeletal muscle and serum FFA concentration seem to be determinants of endothelial function.

Adenosine Triphosphatases↗
PubMed2001

Diurnal variations of the dominant cycle length of chronic atrial fibrillation.

High-resolution digital Holter recording was carried out in 21 patients (15 men, 64 +/- 12 yr) with chronic atrial fibrillation. Dominating atrial cycle length (DACL) was derived by frequency domain analysis of QRST-reduced electrocardiograms. Daytime mean DACL was 150 +/- 17 ms, and nighttime mean was 157 +/- 22 ms (P = 0. 0002). Diurnal fluctuation in DACL differed among patients: it tended to be virtually absent in those with a short mean DACL, but in those with longer DACL the night-day difference was as much as 23 ms (R = 0.72, P < 0.001, correlation of mean DACL to night-day difference). Mean DACL also correlated with ventricular cycle length (R = 0.40, P < 0.001), particularly at night (r = 0.49). The shorter cycle lengths found in this study during the day are consistent with sympathetic and/or other physiological modulation, but since increased vagal tone shortens atrial refractoriness in most models, parasympathetic influences are not likely to play a major role. Alternatively, atrial effective refractory period may not be the sole determinant of atrial cycle length during atrial fibrillation.

Adult↗
PubMed2000

Relationships between muscle morphology and insulin sensitivity are improved after adjustment for intra-individual variability in 70-year-old men.

The purpose of this investigation was to examine to what extent variability in the muscle morphology and insulin sensitivity influence the correlation between them. Reproducibility of muscle characteristics was estimated in duplicate biopsies from the same thigh of 23 subjects from a cohort of 70-year-old men. The coefficient of variation (CV) for different characteristics of muscle morphology was between 11 and 42% in duplicate biopsies. Coefficient of variation for markers of insulin sensitivity ranged between 12 and 39%. The variability reflected by intra-class correlation ranged from 0.23 to 0.60 for muscle morphology and from 0.68 to 0.96 for estimates of insulin sensitivity. The correlation analysis between muscle morphology and insulin resistance was performed in a sample of 515 men from the cohort, correlation coefficients were calculated with (rtrue) and without (r) adjustment for intra-individual variation. Insulin sensitivity showed a positive relationship with percentage of type I fibres (rtrue=0.33, r=0.21; P < 0.0001) and capillary density (rtrue=0.43, r=0.21; P < 0. 0001) and negative correlations with percentage of type IIB fibres (rtrue=-0.35, r=-0.24; P < 0.0001). Capillary density was inversely correlated to insulin. Thus, an obvious improvement of the correlation was seen after correcting intra-individual variation. In conclusion, owing to the low degree of reproducibility of muscle morphology variables and insulin sensitivity, implying a noticeable underestimation of correlations, the r-values should be adjusted for within-subject variation in order to demonstrate a more accurate estimate of the strength of the relationships studied.

Aged↗
PubMed2000

Alterations in skeletal muscle morphology in glucose-tolerant elderly hypertensive men: relationship to development of hypertension and heart rate.

OBJECTIVE: To compare the muscle morphology in hypertensive subjects with that in controls and to test the hypothesis of a relation between heart rate, development of hypertension and muscle morphology that is independent of glucose intolerance. PATIENTS AND METHODS: We studied 43 glucose-tolerant, untreated hypertensive subjects and 113 healthy controls in a longitudinal cohort of 70-year-old men. Metabolic status (oral glucose tolerance test and euglycemic, hyperinsulinaemic clamp test), muscle fibre distribution (myosin ATPase staining) and capillary supply (amylase-PAS method) were evaluated. Blood pressure and heart rate data were available from both ages 50 and 70 years. RESULTS: Hypertensive subjects had a significantly smaller mean number of capillaries per fibre than controls (1.53 versus 1.64; P = 0.04). In hypertensive subjects, the proportions of type I and type II fibres were correlated to mean arterial pressure (r = -0.56 and r= 0.52, respectively, P < 0.05 for both). The increase in mean arterial pressure over 20 years was closely correlated to capillary density in mm2 (r= -0.62; P< 0.0001). Capillary supply was inversely related to resting heart rate both at ages 50 and 70 years. CONCLUSIONS: Skeletal muscle of glucose tolerant hypertensive subjects showed a lower capillary supply than that of controls. This capillary rarefaction was correlated to increase in mean arterial pressure over two decades and to supine heart rate. This is compatible with the suggestion that higher sympathetic drive might generate structural alterations in muscle capillarization.

Aged↗
PubMed2000

Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men.

Endurance trained (n = 14) and untrained young men (n = 15) were compared regarding the fatty acid profile of the vastus lateralis muscle after 8 wk on diets with a similar fatty acid composition. The skeletal muscle phospholipids in the trained group contained lower proportions of palmitic acid (16:0) (-12.4%, P < 0.001) and di-homo-gamma-linolenic acid [20:3(n-6)] (-15.3%, P = 0.018), a lower n-6-to-n-3 ratio (-42.0%, P = 0.015), higher proportions of stearic acid (18:0) (+9.8%, P = 0.004) and sum of n-3 polyunsaturated fatty acids (+33.8%, P = 0.009), and a higher ratio between 20:4(n-6) to 20:3(n-6) (+18.4%, P = 0.006) compared with those in the untrained group. The group differences in 16:0, 20:3(n-6), 18:0/16:0, and 20:4(n-6)/20:3(n-6) were independent of fiber-type distribution. The trained group also showed a lower proportion of 16:0 (-7.9%, P < 0.001) in skeletal muscle triglycerides irrespective of fiber type. In conclusion, the fatty acid profile of the skeletal muscle differed between trained and untrained individuals, although the dietary fatty acid composition was similar. This difference was not explained by different fiber-type distribution alone but appears to be a direct consequence of changes in fatty acid metabolism due to the higher level of physical activity.

Adult↗
PubMed2000

Epidemiological and clinical studies on insulin resistance and diabetes.

In Uppsala, extensive epidemiological and clinical studies on insulin resistance and diabetes have been ongoing for the past 30 years. A prospective cohort study of men born 1920-24, living in Uppsala County, was initiated during 1969-74 (the Uppsala Longitudinal Study of Adult Men, ULSAM). Risk factors for cardiovascular disease were examined in 2,322 men, and re-examinations have been performed every 10 years. At the first follow-up, when the men were 60 years old, insulin resistance was found to be a risk factor for development of hypertension and diabetes. In addition, treatment with antihypertensive medication was an independent risk factor for development of diabetes. These findings resulted in a series of clinical studies on metabolic effects of antihypertensive agents. At the second follow-up, when the men were 70 years old, the development of hypertension and diabetes was once again in focus, but at this time, cross-sectional and prospective studies of other cardiovascular determinants, such as circadian blood pressure pattern, left ventricular geometry and function, muscle morphology, ion status, fibrinolysis and cognitive function, were also performed. The cohort has furthermore been linked to the Swedish census and hospital discharge and cause of death registries, it has been used for studies on relationships between birth weight and cardiovascular disease, and genetic analyses have been performed, taking advantage of the long observation time obtained in this cohort. The cohort is currently being re-examined for the third time, and will hopefully continue to provide valuable information on the epidemiology of diabetes and cardiovascular disease in the future.

Aged↗
PubMed1999

Cardioversion of atrial fibrillation and its effect on right ventricular function as assessed by tricuspid annular motion.

In patients with atrial fibrillation, the reduced right ventricular function determined by tricuspid annular motion before cardioversion returns to normal 1 month after successful cardioversion to sinus rhythm. The simplicity of recording the tricuspid annular motion provides an easy opportunity to assess right ventricular function following electroconversion of atrial fibrillation to sinus rhythm.

Aged↗
PubMed1999

Effect of renal disease and hemodialysis on foscarnet pharmacokinetics and dosing recommendations.

BACKGROUND: Foscarnet is an antiviral agent commonly used for managing patients with cytomegalovirus infection. Despite its clinical usefulness, foscarnet is associated with substantial adverse effects including nephrotoxicity. Moreover, foscarnet is primarily eliminated unchanged through the kidneys, thus requiring aggressive dose adjustment during kidney failure. To develop specific dosage guidelines, information on the disposition of this compound in patients with varying degrees of renal function and those requiring dialysis is essential. DESIGN: Twenty-six subjects were enrolled in this study and divided into five groups depending on their degree of renal dysfunction. Group 1 included subjects with normal renal function; group 5 included subjects requiring maintenance hemodialysis. Nondialysis study subjects received a single 60-mg/kg intravenous dose of foscarnet whereas hemodialysis subjects received two intravenous doses, separated by 1 week, to compare the effects of conventional and high-flux dialysis methods. RESULTS: Mean plasma clearance in control subjects averaged 2.1+/-0.7 ml/minute/kg and declined proportionally with changing renal function as indicated by the regression equation: Clp (ml/minute/kg) = 1.48 [CrCl (ml/minute/kg)]-0.08 (r2 = 0.82). Mean half-life averaged 1.9+/-0.1 hours in normal subjects and increased to a mean of 25+/-19 hours in study subjects with severe impairment not on dialysis. Foscarnet dialysis clearance (based on dialysate recovery) averaged 183 ml/minute with conventional dialysis methods and 253 ml/minute during high-flux procedures, which resulted in removal of 37% and 38% of a dose for the two methods, respectively. CONCLUSIONS: These data indicate that substantial dosage adjustments must be made in renal failure patients. Therefore, a patient-specific dosage nomogram has been developed.

Adult↗
PubMed1998

The stereoisomers quinine and quinidine exhibit a marked stereoselectivity in the inhibition of hepatobiliary transport of cardiac glycosides.

BACKGROUND/AIMS: Certain basic (cationic) drugs are known to interact with the hepatic transport, and renal and/or biliary clearance of cardiac glycosides. The mechanisms behind these interactions are not fully understood. In the present study our aim was to investigate the effects of the two diastereomers, quinidine and quinine, as well as the calcium antagonist verapamil, on the hepatobiliary elimination of digoxin and ouabain in the isolated perfused rat liver. METHODS: Livers from male, fasting Wistar rats were perfused by recirculation of Krebs-Henseleit bicarbonate buffer supplemented with 1% BSA. Disposition of digoxin or ouabain was studied at an initial perfusion medium concentration (Ci) of 100 or 10 nmol/l for digoxin and a Ci of 30 micromol/l for ouabain. The Ci of quinine, quinidine or verapamil was 50 micromol/l. Concentrations of the drugs in perfusion medium and bile were followed up to 2 h. RESULTS: A marked reduction in the initial medium disappearance rate of digoxin and ouabain by quinine was found, whereas quinidine did not affect the hepatic disposition of the cardiac glycosides. The stereoselective inhibition of digoxin and ouabain clearance by quinine, and not by quinidine, was shown to be due to an effect on the hepatic uptake level rather than on the metabolic conversion and/or the biliary excretion steps. An allosteric type of inhibition by the basic drugs, exerted from the inside of the cells, is inferred. This interaction may occur at the sinusoidal plasma membrane on the level of multi-specific carrier proteins for cardiac glycosides and cationic drugs, as cloned recently by various groups. CONCLUSIONS: A marked stereoselective difference was found in the effect of the stereoisomers quinidine and quinine on the hepatic uptake of digoxin and ouabain, quinine being the potent inhibitor.

Animals↗
PubMed1998

Stereoselective inhibition by the diastereomers quinidine and quinine of uptake of cardiac glycosides into isolated rat hepatocytes.

The pharmacokinetic interaction between quinidine and digoxin in patients is well-known, in general requiring a dose reduction of digoxin in patients concomitantly treated with quinidine. Quinine, the diastereomer of quinidine, has not been as extensively studied in this respect. In addition to an interaction with the renal clearance of digoxin by quinidine, both diastereomers have been reported to inhibit the biliary clearance of digoxin in man. To further investigate the mechanisms of these hepatobiliary transport interactions at the cellular level, we compared the effects of quinidine and quinine, as well as of the calcium antagonist verapamil, on the uptake of digoxin and ouabain in isolated rat hepatocytes. Initial uptake rates of digoxin and ouabain were determined in the presence of various concentrations of quinine and quinidine. A concentration dependent inhibition of the cellular uptake of both cardiac glycosides by quinine and quinidine was found, quinine being a more potent inhibitor than quinidine. Our results indicate a stereoselective inhibition of the hepatocellular uptake by the two diastereomers quinidine and quinine, the latter being about equipotent to verapamil. This unequal inhibitory potency of the two basic drugs was detected earlier in oocyte studies with the cloned organic cation transporter OCT1.

Animals↗
PubMed1997

Comparison of pharmacokinetics and dynamics of two dosage regimens of foscarnet in AIDS patients with Cytomegalovirus retinitis.

OBJECTIVE: To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis. METHODS: Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively. RESULTS: The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together. CONCLUSION: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period.

AIDS-Related Opportunistic Infections↗
PubMed1997

Prevalence and treatment of chronic idiopathic thrombocytopenic purpura of childhood in Sweden.

The frequency and treatment of children with chronic idiopathic thrombocytopenic purpura in Sweden were characterized using a national enquiry based on a questionnaire. Seventy-five children diagnosed as having chronic idiopathic thrombocytopenic purpura on 1 September 1993 were identified. The prevalence in children between 0.5 and 15.5 years of age was calculated to be 4.6/100,000. The median age at the time of diagnosis was 5 years and the male/female ratio was 1:1.2. Almost half of the patients (43%) were not treated at all during the disease. Steroids (43%) and intravenous immunoglobulin (25%) were most commonly used. Only two children were splenectomized.

Adolescent↗