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Biomedical subjects

Jesper Sonne

Publications and source records attributed to Jesper Sonne.

11 recordsLinked to original sources
PubMed2005

Reliability of a modified medication appropriateness index in primary care.

OBJECTIVE: To evaluate the inter-group and intra-group reliability of a modified Medication Appropriateness Index (MAI) for use in primary care. METHODS: Elderly (>65 years) polypharmacy (> or =5 drugs) patients in Copenhagen County participated in the study. Information concerning their medical history and information regarding each drug taken by them was provided by their own general practitioners. A MAI was scored by two groups of evaluators for every drug. To evaluate inter-group agreement, 211 drugs taken by 30 patients were rated according to the ten criteria making up the MAI. Both evaluator groups provided summaries of comments on the medication of each patient. Intra-group agreement was determined from MAI ratings performed twice at two different times on 86 drugs taken by ten patients. Agreement and chance-adjusted agreement were determined, the latter through kappa statistics. The proportion of positive (ppos) and negative (pneg) agreement was also determined. RESULTS: The overall chance-adjusted inter-group agreement (kappa) was moderate. The agreement was good on the criteria practical directions and drug-disease interaction, moderate on the criteria dosage and duration, fair on the criteria indication, effectiveness, duplication and expense, and poor on the criterion drug-drug interaction. The overall chance-adjusted intra-group agreement was good for all criteria and very good for the criteria indication and practical directions. CONCLUSION: The MAI is used to quantify appropriate and inappropriate prescribing and changes in prescribing quality in intervention studies. However, caution should be used when comparing results across different settings and evaluators. Our study suggests that the index should only be used in intervention studies if the same group rates the appropriateness pre- and post-intervention.

Aged↗
PubMed2005

Enalapril dosage in progressive chronic nephropathy: a randomised, controlled trial.

OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken. METHODS: Forty patients with a median glomerular filtration rate (GFR) of 17 (6-35) ml/min/1.73 m2 were studied in an open-label, randomised trial comparing patients with a high (>50 ng/ml) with patients with a low (<10 ng/ml) target trough plasma concentration of enalaprilat. The dose of enalapril was titrated accordingly. The patients were followed for 12 months or until they needed renal replacement therapy. GFR was measured at 3-month intervals by the plasma clearance of 51Cr-EDTA, and the individual rates of progression of renal failure were calculated as the slope of GFR versus time plot. RESULTS: In the high-concentration group, the median enalaprilat trough concentration was 92.9 ng/ml (21.8-371.0 ng/ml) and in the low-concentration group it was 9.1 ng/ml (2.5-74.8 ng/ml) at 3 months follow-up (P<0.001). The median daily doses of enalapril were 10 mg (2.5-30 mg) and 1.88 mg (1.25-5 mg) in the high and low groups, respectively (P<0.001). In the high-concentration group, the mean+/-SE decline in renal function was 6.1+/-1.5 ml/min/1.73 m2 per year and in the low-concentration group it was 4.3+/-14.4 ml/min/1.73 m2 per year (P=0.48). Five patients in the high-concentration group reached end-stage renal failure whereas none in the low-concentration group did (P=0.04). There were no statistically significant differences in blood pressure level, concomitant antihypertensive therapy or urinary albumin excretion. However, the high-enalaprilat concentration group had an overall higher plasma potassium concentration of 0.42 mmol/l than the low group (P<0.001). CONCLUSION: In patients with moderate to severe renal insufficiency, a low concentration of enalaprilat afforded the same degree of renoprotection, blood pressure control and minimisation of proteinuria as a high concentration, during 12 months of follow-up. The high-dosage treatment was associated with a more pronounced tendency to hyperkalaemia. Thus, there seems to be no indication for increasing the daily dose of enalapril beyond what achieves adequate blood pressure control in this group of patients.

Adult↗
PubMed2004

Oral manganese for liver imaging at three different field strengths.

RATIONALE AND OBJECTIVES: To study the magnetic resonance imaging signal intensity of the liver and gall bladder before and after ingestion of a new oral manganese containing contrast medium at three different field strengths. MATERIALS AND METHODS: Twelve healthy male volunteers (mean age, 24.9 years; range, 20-39 years) underwent abdominal magnetic resonance imaging (T(2)W COR, T(1)W COR, T(1)W TRA) at 0.23 T, 0.6 T, and 1.5 T before and after the contrast administration. The duration of fasting was identical before the two studies. Volunteers were randomized into two equal groups (n = 6) to ingest either half or full strength CMC-001 providing either 0.8 or 1.6.g MnCl(2) plus absorption promoters. The CMC-001 dose was dissolved in 400 mL water and ingested 2.5 hours before imaging. The resulting images were evaluated with regard to visualization of the liver and the gall bladder by three radiologists. The signal intensity of the liver was also measured. Blood and urine samples were collected before and after ingestion of CMC-001. RESULTS: The intake of CMC-001 caused a significant increase in the signal intensity of the liver at all three field strengths and at both dosages (up to 90%) on the T(1)W images. The internal structure of the liver was significantly better delineated. The bile in gall bladder was bright after ingestion of the low dose, but dark after the full dose. On the T(2)W images, CMC-001 lowered the signal intensity of liver with up to 30%. CMC-001 had a slight metallic taste, but of no importance according to the volunteers. No systematic adverse reactions caused by the contrast medium were registered. No changes in the blood levels of various routine parameters were measured. CONCLUSION: It is possible to increase the signal intensity of the liver significantly by oral intake of essential nutritional elements including manganese. The imaging window is more than 2 hours.

Administration, Oral↗
PubMed2004

Fluoroquinolone antibiotics in a hospital sewage line; occurrence, distribution and impact on bacterial resistance.

In hospital sewage lines, human faecal bacteria are exposed to antibiotics, posing a risk for selection of antibiotic resistant microorganisms. We constructed a system for continuous sampling in a hospital sewage line that allowed us to study longitudinal establishment of bacteria, concentrations of antibiotics, and selection of bacterial resistance in waste water, sediment and biofilm. The focus in this study was on fluoroquinolones, a widely used group of antibiotics with increasing resistance problems. We found low levels of ciprofloxacin and ofloxacin in waste water but high concentrations in sediment. Despite the high levels of fluoroquinolones bound to sediment, we did not find any development of resistance against fluoroquinolones in Enterobacteriacae spp. and faecal enterococci isolated from sediment.

Drug Resistance, Bacterial↗
PubMed2003

Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity.

OBJECTIVE: To study the distribution of the thiopurine methyltransferase (TPMT) genotype among azathioprine (Aza)-tolerant and -intolerant patients with various disorders, and to investigate a possible relationship with the Aza metabolite levels. METHODS: Forty-six Aza-tolerant and six Aza-intolerant patients had the TPMT genotype distribution determined using a polymerase chain reaction (PCR) assay and the forty-six Aza-tolerant patients had the Aza metabolite levels determined using a high-pressure liquid chromatography (HPLC) analysis. RESULTS: One non-functional TPMT mutant allele was demonstrated in 2 of the 46 Aza-tolerant patients (4.4%) and one or two non-functional mutant alleles in 2 of the 6 Aza-intolerant patients (33.3%). Of the 4 patients, with one or two non-functional mutant alleles 2 (50%) were intolerant to Aza compared with 4 of the 48 patients (8.3%) with no mutations detected. The time to hepatotoxicity did not differ significantly between the 2 patients with one or two non-functional mutant alleles and the remaining 3 patients ( P=0.5). The TPMT genotype distribution differed slightly in the three different categories of disorders ( P=0.05). The median E-6-TGN level among the 2 TPMT heterozygous patients was 275 pmol/8x10(8) RBC (range 240-310), whereas the remaining 44 patients had a median E-6-TGN level of 110 pmol/8x10(8) RBC (range 0-440) ( P=0.07). CONCLUSION: Although TPMT genotyping cannot be recommended on behalf of the present study, it is to be expected that half of the patients with one or two non-functional TPMT mutant alleles will develop Aza intolerance leading to withdrawal of therapy. Thus, clinicians may anticipate about 5% of the patients to develop intolerance to Aza therapy solely for that reason.

Adjuvants, Immunologic↗
PubMed2003

Blood pressure response to conventional and low-dose enalapril in chronic renal failure.

AIMS: In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. METHODS: As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data were analysed in all patients completing 3 months of follow-up. The patients were allocated to two trough plasma concentrations of enalaprilat, either above 50 ng ml(-1) (high) (n = 17) or below 10 ng ml(-1) (low) (n = 18), and the daily dose of enalapril titrated accordingly. RESULTS: Median (range) glomerular filtration rate (GFR) at baseline was 18 (7.9) in the high enalaprilat concentration group and 17 (7.3) ml min(-1) 1.73 m(2) in the low concentration group (NS). Nine patients in each group were on treatment with enalapril at baseline with a median daily dose of 5 mg in both the high (5-10) and low (2.5-20) concentration group. At 3 months' follow-up, the dose was 10 (2.5-30) and 1.9 (1.25-5) mg (P < 0.0001), respectively. After 3 months median trough concentrations of enalaprilat were 82.5 (22-244) ng ml(-1) and 9.1 (2.5-74.8) ng ml(-1) (P < 0.002). At baseline the median systolic blood pressures in the two groups were 140 (110-200) and 133 (110-165), in the high and low enalaprilat concentration groups, respectively, and after 3 months they were 135 (105-170) and 130 (105-170) mmHg (NS). Median diastolic blood pressure was 80 mmHg in each group both at baseline (65-100) and at follow-up (60-95) (NS). There was no difference between the groups in concomitant antihypertensive treatment (number of patients treated, mean daily dose) during the observation period. Proteinuria remained stable during the study period in both groups; patients in the high concentration group had higher plasma potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR. CONCLUSIONS: In moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective of concomitant antihypertensive treatment.

Adult↗
PubMed2002

[Why is QT interval interesting?].

A prolonged Q-T interval is generally associated with increased risk of ventricular arrhythmias, like torsade de pointes, and death. It has recently become apparent that not only antiarrhythmic drugs such as sotalol and Kinidin, but also a variety of nonantiarrhythmic drugs, like certain antihistamines, antimicrobial drugs, psychiatric drugs, and cisapride, may induce prolongation of the Q-T interval and torsade de pointes. Special concern should be drawn to the co-administration of drugs that interfere with the metabolism and elimination of these drugs, such as ketoconazole. Patients with congenital long Q-T syndrome, patients with heart disease, with hypokalaemia or hypomagnesaemia, and women have an increased risk. Every sign on dizziness or syncope should be regarded as a warning sign of possible arrhythmia in patients treated with drugs that potentially prolong the Q-T interval. Measurement of the Q-T interval before and during treatment is generally recommended in high-risk patients.

Anti-Arrhythmia Agents↗
PubMed2002

Intestinal first pass metabolism of midazolam in liver cirrhosis --effect of grapefruit juice.

AIMS: Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a reduced intestinal first pass metabolism and thereby an increased oral bioavailability of certain drugs. For example, it has been shown that the oral bioavailability of midazolam, a CYP3A4 substrate, increased by 52% in healthy subjects after ingestion of grapefruit juice. However, this interaction has not been studied in patients with impaired liver function. Accordingly, the effect of grapefruit juice on the AUC of midazolam and the metabolite alpha-hydroxymidazolam was studied in patients with cirrhosis of the liver. METHODS: An open randomized two-way crossover study was performed. Ten patients (3 females, 7 males) with liver cirrhosis based on biopsy or clinical criteria participated. Six patients had a Child-Pugh score of A, one B and three C. Tap water (200 ml) or grapefruit juice were consumed 60 and 15 min before midazolam (15 mg) was administered orally. Plasma samples were analysed for midazolam and alpha-hydroxymidazolam. RESULTS: Grapefruit juice increased the AUC of midazolam by 106% (16, 197%) (mean (95% confidence interval)) and the AUC of the metabolite alpha-hydroxymidazolam decreased to 25% (12, 37%) (P<0.05 for both). The ratio of the AUCs of the metabolite alpha-hydroxymidazolam to midazolam decreased from 0.77 (0.46, 1.07) to 0.11 (0.05, 0.19) (P<0.05). t(1/2) remained unaltered for both drug and metabolite. Midazolam C(max), t(max), and alpha-hydroxymidazolam t(max) increased, but these changes were not statistically significant, whereas C(max) of the metabolite decreased to 30% (14, 47%) (P<0.05). CONCLUSIONS: A marked interaction between oral midazolam and grapefruit juice was found and the data are consistent with a reduced first-pass metabolism of midazolam. This is likely to occur at the intestinal wall inhibition of CYP3A4 activity by grapefruit juice. These results indicate that patients with liver cirrhosis are more dependent on the intestine for metabolism of CYP3A4 substrates than subjects with normal liver function.

Adult↗
PubMed2002

Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans.

OBJECTIVE: Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes. METHODS: Twelve healthy subjects who lived at sea level were exposed to altitude-induced hypoxia for 7 days at 4559 m above sea level. Hepatic CYP enzyme activity was measured before departure, at 24 and 96 hours after arrival to high-altitude location, and at 1 month after return to sea level. CYP enzyme activities were measured by means of the metabolic ratios of sparteine (CYP2D6), endogenous cortisol metabolism (CYP3A4), and caffeine (CYP1A2), as well as by the S/R ratio of mephenytoin (CYP2C19) and antipyrine clearance. RESULTS: The metabolic ratio of sparteine increased after 24 hours at high altitude (median difference, 0.15; 95% confidence interval, 0.05 to 0.28) and remained increased after 96 hours. The ratio decreased after return to sea level (median difference, -0.15; 95% confidence interval, -0.29 to -0.03; P =.016, Friedman test). The metabolic ratio of cortisol decreased after 24 hours (median difference, -2.0; 95% confidence interval, -3.5 to -0.5) but returned to sea level values after 96 hours at high altitude (median difference, 1.6; 95% confidence interval, 1.0 to 4.2; P =.047, Friedman test). These changes indicate a small decrease in the activity of CYP2D6 and CYP3A4. There were no significant changes regarding the metabolic ratio of caffeine, the S/R ratio of mephenytoin, or antipyrine clearance. CONCLUSION: The small changes observed suggest that acute hypoxia has no clinically significant effects on CYP enzymes in humans.

Acute Disease↗