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Biomedical subjects

A Hedman

Publications and source records attributed to A Hedman.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1995

Renal elimination of ceftazidime during pregnancy.

OBJECTIVE: Our purpose was to study the pharmacokinetics of ceftazidime at different stages of pregnancy and in the nonpregnant state to determine whether glomerular filtration rate is altered and whether tubular secretions occurs. STUDY DESIGN: Twelve pregnant women with asymptomatic bacteruria were given a bolus dose of 400 mg of ceftazidime followed by a constant infusion for 4 hours. Inulin was infused simultaneously to determine glomerular filtration rate. Blood samples were drawn every 30 minutes. Urine was collected immediately after the bolus dose and then every hour. The same study procedure was then repeated twice: 2 weeks before the expected delivery and after termination of breast-feeding. RESULTS: At term clearance values were raised by 50% to 100% compared with the values found in the postpartum period. At all observation points a close correlation between inulin and ceftazidime clearance values were found. CONCLUSION: The results strongly indicate that ceftazidime is excreted exclusively by glomerular filtration with no tubular reabsorption. During pregnancy the excretion pattern is unaltered, but renal elimination is increased.

Bacteriuria↗
PubMed1993

Dose proportional absorption of 25-150 mg atenolol.

We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.

Administration, Oral↗
PubMed1992

Inhibition by basic drugs of digoxin secretion into human bile.

Bile samples from previous interaction studies in man were re-analysed by a combined HPLC/radioimmunoassay method. Quinidine, quinine and verapamil but not probenecid or spironolactone were found to inhibit the biliary secretion of unchanged digoxin.

Bile↗
PubMed1992

Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance.

The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg.d-1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 x oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P = 0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance.

Adult↗
PubMed1991

Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans.

The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.

Bile↗
PubMed1991

No effect of probenecid on the renal and biliary clearances of digoxin in man.

1. The cardiac glycoside digoxin is subject to a number of pharmacokinetic interactions. This study concerns the influence of the anionic transport inhibitor probenecid on the steady-state kinetics of digoxin. 2. Six healthy young men were enrolled in the study. After an administration period of 6 days with digoxin only (0.5 to 1 mg p.o. day-1) or digoxin in combination with probenecid (2 g p.o. day-1; 8 days), digoxin was administered intravenously (0.7 oral dose) on day 7. Plasma and urine samples were taken over 48 h. The biliary clearance of digoxin was measured during day 8 by a duodenal perfusion technique. 3. Probenecid did not affect the plasma clearance (mean +/- s.d.: 255 +/- 80 vs 266 +/- 40 ml min-1), renal clearance (166 +/- 17 vs 155 +/- 10 ml min-1), biliary clearance (106 +/- 40 vs 111 +/- 50 ml min-1), elimination half-life (34.4 vs 35.2 h) or volume of distribution (538 +/- 241 vs 566 +/- 60 l) of digoxin. 4. Our results suggest that different systems exist in man for the renal and biliary secretion of probenecid and digoxin.

Administration, Oral↗
PubMed1991

Decreased renal clearance of sodium in cystic fibrosis.

In 10 patients with cystic fibrosis (CF) and 10 controls of similar age quantitative segmental handling of sodium was estimated by lithium clearance. In the CF group, there was a tendency for an increased glomerular filtration rate (GFR) and increased absolute proximal sodium reabsorption. The fractional distal sodium reabsorption was significantly (p = 0.015) increased and sodium clearance was significantly (p less than 0.01) decreased in CF.

Adult↗